Interleukin 15: biology and relevance to human disease

Blood - Tập 97 Số 1 - Trang 14-32 - 2001
Todd A. Fehniger1, Michael A. Caligiuri1
1From the Departments of Internal Medicine and Molecular Virology, Immunology, and Medical Genetics, Divisions of Hematology/Oncology and Human Cancer Genetics, and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH.

Tóm tắt

Từ khóa


Tài liệu tham khảo

Grabstein, 1994, Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor., Science., 264, 965, 10.1126/science.8178155

Burton, 1994, A lymphokine, provisionally designated interleukin T and produced by a human adult T-cell leukemia line, stimulates T-cell proliferation and the induction of lymphokine-activated killer cells., Proc Natl Acad Sci U S A., 91, 4935, 10.1073/pnas.91.11.4935

Bamford, 1994, The interleukin (IL) 2 receptor beta chain is shared by IL-2 and a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells., Proc Natl Acad Sci U S A., 91, 4940, 10.1073/pnas.91.11.4940

Bamford, 1996, Interleukin (IL) 15/IL-T production by the adult T-cell leukemia cell line HuT-102 is associated with a human T-cell lymphotrophic virus type I region /IL-15 fusion message that lacks many upstream AUGs that normally attenuates IL-15 mRNA translation., Proc Natl Acad Sci U S A., 93, 2897, 10.1073/pnas.93.7.2897

Bazan, 1990, Haemopoietic receptors and helical cytokines., Immunol Today., 11, 350, 10.1016/0167-5699(90)90139-Z

Bazan, 1990, Structural design and molecular evolution of a cytokine receptor superfamily., Proc Natl Acad Sci U S A., 87, 6934, 10.1073/pnas.87.18.6934

Carson, 1994, Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor., J Exp Med., 180, 1395, 10.1084/jem.180.4.1395

Kennedy, 2000, Reversible defects in natural killer and memory CD8 T cell lineages in IL-15 deficient mice., J Exp Med., 191, 771, 10.1084/jem.191.5.771

Lodolce, 1998, IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation., Immunity., 9, 669, 10.1016/S1074-7613(00)80664-0

Anderson, 1995, Chromosomal assignment and genomic structure of IL-15., Genomics., 25, 701, 10.1016/0888-7543(95)80013-C

Krause, 1996, Genomic structure and chromosomal localization of the human interleukin 15 gene (IL-15)., Cytokine., 8, 667, 10.1006/cyto.1996.0089

Meazza, 1996, Identification of a novel interleukin-15 (IL-15) transcript isoform generated by alternative splicing in human small cell lung cancer cell lines., Oncogene., 12, 2187

Onu, 1997, Regulation of IL-15 secretion via the leader peptide of two IL-15 isoforms., J Immunol., 158, 255, 10.4049/jimmunol.158.1.255

Tagaya, 1997, Generation of secretable and nonsecretable interleukin 15 isoforms through alternate usage of signal peptides., Proc Natl Acad Sci U S A., 94, 14444, 10.1073/pnas.94.26.14444

Nishimura, 1998, Translational efficiency is up-regulated by alternative exon in murine IL-15 mRNA., J Immunol., 160, 936, 10.4049/jimmunol.160.2.936

Prinz, 1998, Alternative splicing of mouse IL-15 is due to the use of an internal splice site in exon 5., Brain Res Mol Brain Res., 63, 155, 10.1016/S0169-328X(98)00284-8

Seigel, 1984, Gene for T-cell growth factor: location on human chromosome 4q and feline BI., Science., 223, 175, 10.1126/science.6318318

Smith, 1988, Interleukin-2: inception, impact, and implications., Science., 240, 1169, 10.1126/science.3131876

Meazza, 1997, Expression of two interleukin-15 mRNA isoforms in human tumors does not correlate with secretion: role of different signal peptides., Eur J Immunol., 27, 1049, 10.1002/eji.1830270502

Gaggero, 1999, Differential intracellular trafficking, secretion, and endosomal localization of two IL-15 isoforms., Eur J Immunol., 29, 1265, 10.1002/(SICI)1521-4141(199904)29:04<1265::AID-IMMU1265>3.0.CO;2-V

Kurys, 2000, The long signal peptide isoform and its alternative processing direct the intracellular trafficking of IL-15., J Biol Chem., 275, 30653, 10.1074/jbc.M002373200

Nishimura, 2000, Differential roles of interleukin 15 mRNA isoforms generated by alternative splicing in immune responses in vivo., J Exp Med., 191, 157, 10.1084/jem.191.1.157

Pettit, 1997, Structure-function studies of interleukin 15 using site-specific mutagenesis, polyethylene glycol conjugation, and homology modeling., J Biol Chem., 272, 2312, 10.1074/jbc.272.4.2312

Minami, 1993, The IL-2 receptor complex: its structure, function, and target genes., Annu Rev Immunol., 11, 245, 10.1146/annurev.iy.11.040193.001333

Waldmann, 1998, Interleukin-2, interleukin-15, and their receptors., Int Rev Immunol., 16, 205, 10.3109/08830189809042995

He, 1998, The structure and function of gamma c-dependent cytokines and receptors: regulation of T lymphocyte development and homeostasis., Crit Rev Immunol., 18, 503, 10.1615/CritRevImmunol.v18.i6.20

Uribe, 1998, X-linked SCID and other defects of cytokine pathways., Semin Hematol., 35, 299

Giri, 1994, Utilization of the beta and gamma chains of the IL-2 receptor by the novel cytokine IL-15., EMBO J., 13, 2822, 10.1002/j.1460-2075.1994.tb06576.x

Giri, 1995, Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor., EMBO J., 14, 3654, 10.1002/j.1460-2075.1995.tb00035.x

Anderson, 1995, Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genes., J Biol Chem., 270, 29862, 10.1074/jbc.270.50.29862

Dubois, 1999, Natural splicing of exon 2 of human interleukin-15 receptor alpha-chain mRNA results in a shortened form with a distinct pattern of expression., J Biol Chem., 274, 26978, 10.1074/jbc.274.38.26978

Kennedy, 1996, Characterization of interleukin-15 (IL-15) and the IL-15 receptor complex., J Clin Immunol., 16, 134, 10.1007/BF01540911

Tagaya, 1996, Identification of a novel receptor/signal transduction pathway for IL-15/T in mast cells., EMBO J., 15, 4928, 10.1002/j.1460-2075.1996.tb00873.x

Di Santo, 1995, Common cytokine receptor gamma chain (gamma c)-dependent cytokines: understanding in vivo functions by gene targeting., Immunol Rev., 148, 19, 10.1111/j.1600-065X.1995.tb00091.x

Leonard, 1995, Role of the common cytokine receptor gamma chain in cytokine signaling and lymphoid development., Immunol Rev., 148, 97, 10.1111/j.1600-065X.1995.tb00095.x

Di Santo, 1998, Natural killer and T cells of innate and adaptive immunity: lymphoid compartments with different requirements for common gamma chain-dependent cytokines., Immunol Rev., 165, 29, 10.1111/j.1600-065X.1998.tb01227.x

He, 1998, The structure and function of gamma c-dependent cytokines and receptors: regulation of T lymphocyte development and homeostasis., Crit Rev Immunol., 18, 503, 10.1615/CritRevImmunol.v18.i6.20

Malek, 1999, Multiple gamma c-dependent cytokines regulate T-cell development., Immunol Today., 20, 71, 10.1016/S0167-5699(98)01391-7

Taniguchi, 1995, IL-2 signaling involves recruitment and activation of multiple protein tyrosine kinases by the IL-2 receptor., Ann NY Acad Sci., 766, 235, 10.1111/j.1749-6632.1995.tb26671.x

Ihle, 1995, Signaling through the hematopoietic cytokine receptors., Annu Rev Immunol., 13, 369, 10.1146/annurev.iy.13.040195.002101

Miyazaki, 1994, Functional activation of Jak1 and Jak3 by selective association with IL- 2 receptor subunits., Science., 266, 1045, 10.1126/science.7973659

Lin, 1995, The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15., Immunity., 2, 331, 10.1016/1074-7613(95)90141-8

Miyazaki, 1995, Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc, and lck cooperate in hematopoietic cell proliferation., Cell., 81, 223, 10.1016/0092-8674(95)90332-1

McDonald, 1998, Interleukin-15 (IL-15) induces NF-kappaB activation and IL-8 production in human neutrophils., Blood., 92, 4828, 10.1182/blood.V92.12.4828

Stevens, 1997, Interleukin-15 signals T84 colonic epithelial cells in the absence of the interleukin-2 receptor beta-chain., Am J Physiol., 272, G1201

Tagaya, 1996, IL-15: a pleiotropic cytokine with diverse receptor/signaling pathways whose expression is controlled at multiple levels., Immunity., 4, 329, 10.1016/S1074-7613(00)80246-0

Masuda, 2000, Interleukin-15 induces rapid tyrosine-phosphorylation of STAT6 and the expression of interleukin-4 in mouse mast cells., J Biol Chem., 275, 29331, 10.1074/jbc.M910290199

Carson, 1995, Endogenous production of interleukin 15 by activated human monocytes is critical for optimal production of interferon-gamma by natural killer cells in vitro., J Clin Invest., 96, 2578, 10.1172/JCI118321

Doherty, 1996, Induction and regulation of IL-15 expression in murine macrophages., J Immunol., 156, 735, 10.4049/jimmunol.156.2.735

Blauvelt, 1996, Interleukin-15 mRNA is expressed by human keratinocytes, Langerhans cells, and blood-derived dendritic cells and is downregulated by ultraviolet B radiation., J Invest Dermatol., 106, 1047, 10.1111/1523-1747.ep12338641

Jonuleit, 1997, Induction of IL-15 messenger RNA and protein in human blood-derived dendritic cells: a role for IL-15 in attraction of T cells., J Immunol., 158, 2610, 10.4049/jimmunol.158.6.2610

Mrozek, 1996, Role of interleukin-15 in the development of human CD56+ natural killer cells from CD34+ hematopoietic progenitor cells., Blood., 87, 2632, 10.1182/blood.V87.7.2632.bloodjournal8772632

Leclercq, 1996, Differential effects of interleukin-15 and interleukin-2 on differentiation of bipotential T/natural killer progenitor cells., J Exp Med., 184, 325, 10.1084/jem.184.2.325

Murray, 1998, Cytokine gene expression in murine fetal intestine: potential for extrathymic T cell development., Cytokine., 10, 337, 10.1006/cyto.1997.0302

Mohamadzadeh, 1995, Ultraviolet B radiation up-regulates the expression of IL-15 in human skin., J Immunol., 155, 4492, 10.4049/jimmunol.155.9.4492

Kawai, 1998, Requirement of the IL-2 receptor beta chain for the development of Vgamma3 dendritic epidermal T cells., J Invest Dermatol., 110, 961, 10.1046/j.1523-1747.1998.00214.x

Kumaki, 1996, Expression of interleukin-15 and its receptor by human fetal retinal pigment epithelial cells., Curr Eye Res., 15, 876, 10.3109/02713689609017629

Reinecker, 1996, Intestinal epithelial cells both express and respond to interleukin 15., Gastroenterology., 111, 1706, 10.1016/S0016-5085(96)70036-7

Weiler, 1998, Interleukin-15, a leukocyte activator and growth factor, is produced by cortical tubular epithelial cells., J Am Soc Nephrol., 9, 1194, 10.1681/ASN.V971194

Lee, 1996, Interleukin-15 gene expression in human astrocytes and microglia in culture., Neuroreport., 7, 1062, 10.1097/00001756-199604100-00022

Azimi, 1998, Human T cell lymphotropic virus type I Tax protein trans-activates interleukin 15 gene transcription through an NF-kappaB site., Proc Natl Acad Sci U S A., 95, 2452, 10.1073/pnas.95.5.2452

Waldmann, 1999, The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens., Annu Rev Immunol., 17, 19, 10.1146/annurev.immunol.17.1.19

Ogasawara, 1998, Requirement for IRF-1 in the microenvironment supporting development of natural killer cells., Nature., 391, 700, 10.1038/35636

Ohteki, 1998, The transcription factor interferon regulatory factor 1 (IRF-1) is important during the maturation of natural killer 1.1+ T cell receptor- alpha/beta+ (NK1+ T) cells, natural killer cells, and intestinal intraepithelial T cells., J Exp Med., 187, 967, 10.1084/jem.187.6.967

Washizu, 1998, The NF-kappaB binding site is essential for transcriptional activation of the IL-15 gene., Immunogenetics., 48, 1, 10.1007/s002510050393

Kozak, 1992, Regulation of translation in eukaryotic systems., Annu Rev Cell Biol., 8, 197, 10.1146/annurev.cb.08.110192.001213

Bamford, 1998, The 5′ untranslated region, signal peptide, and the coding sequence of the carboxyl terminus of IL-15 participate in its multifaceted translational control., J Immunol., 160, 4418, 10.4049/jimmunol.160.9.4418

Musso, 1999, Human monocytes constitutively express membrane-bound, biologically active, and interferon-gamma-upregulated interleukin-15., Blood., 93, 3531, 10.1182/blood.V93.10.3531.410k32_3531_3539

Neely, 1999, Differential expression of interleukin-15 isoforms in resting human PBMC., FASEB J., 13, A1124

Carson, 1997, A potential role for interleukin-15 in the regulation of human natural killer cell survival., J Clin Invest., 99, 937, 10.1172/JCI119258

Zhang, 1998, Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15., Immunity., 8, 591, 10.1016/S1074-7613(00)80564-6

Fearon, 1996, The instructive role of innate immunity in the acquired immune response., Science., 272, 50, 10.1126/science.272.5258.50

Trinchieri, 1989, Biology of natural killer cells., Adv Immunol., 47, 187, 10.1016/S0065-2776(08)60664-1

Robertson, 1990, Biology and clinical relevance of human natural killer cells., Blood., 76, 2421, 10.1182/blood.V76.12.2421.2421

Bancroft, 1993, The role of natural killer cells in innate resistance to infection., Curr Opin Immunol., 5, 503, 10.1016/0952-7915(93)90030-V

Biron, 1995, Effects of IL-12 on immune responses to microbial infections: a key mediator in regulating disease outcome., Curr Opin Immunol., 7, 485, 10.1016/0952-7915(95)80093-X

Biron, 1997, Activation and function of natural killer cell responses during viral infections., Curr Opin Immunol., 9, 24, 10.1016/S0952-7915(97)80155-0

Scharton-Kersten, 1997, Role of natural killer cells in innate resistance to protozoan infections., Curr Opin Immunol., 9, 44, 10.1016/S0952-7915(97)80157-4

Trinchieri, 1997, Cytokines acting on or secreted by macrophages during intracellular infection (IL-15, IL-12, IFN-gamma)., Curr Opin Immunol., 9, 17, 10.1016/S0952-7915(97)80154-9

Colonna, 1997, Specificity and function of immunoglobulin superfamily NK cell inhibitory and stimulatory receptors., Immunol Rev., 155, 127, 10.1111/j.1600-065X.1997.tb00945.x

Raulet, 1999, Development and tolerance of natural killer cells., Curr Opin Immunol., 11, 129, 10.1016/S0952-7915(99)80023-5

Kaplan, 1998, Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice., Proc Natl Acad Sci U S A., 95, 7556, 10.1073/pnas.95.13.7556

Kumar, 1974, Mechanisms of genetic resistance to Friend virus leukemia in mice. I. Role of 89-Sr-sensitive effector cells responsible for rejection of bone marrow allografts., J Exp Med., 139, 1093, 10.1084/jem.139.5.1093

Kumar, 1979, Natural killer cells in mice treated with 89strontium: normal target-binding cell numbers but inability to kill even after interferon administration., J Immunol., 123, 1832, 10.4049/jimmunol.123.4.1832

Seaman, 1979, Natural killer cells, bone, and the bone marrow: studies in estrogen-treated mice and in congenitally osteopetrotic (mi/mi) mice., J Immunol., 122, 2541, 10.4049/jimmunol.122.6.2541

Pollack, 1992, Production and differentiation of NK lineage cells in long-term bone marrow cultures in the absence of exogenous growth factors., Cell Immunol., 139, 352, 10.1016/0008-8749(92)90077-3

Shibuya, 1995, Lymphokine requirement for the generation of natural killer cells from CD34+ hematopoietic progenitor cells., Blood., 85, 3538, 10.1182/blood.V85.12.3538.bloodjournal85123538

Lotzova, 1993, Genesis of human oncolytic natural killer cells from primitive CD34+CD33− bone marrow progenitors., J Immunol., 150, 5263, 10.4049/jimmunol.150.12.5263

Miller, 1992, The generation of human natural killer cells from CD34+/DR− primitive progenitors in long-term bone marrow culture., Blood., 80, 2182, 10.1182/blood.V80.9.2182.2182

Miller, 1994, Differentiation of natural killer (NK) cells from human primitive marrow progenitors in a stroma-based long-term culture system: identification of a CD34+7+ NK progenitor., Blood., 83, 2594, 10.1182/blood.V83.9.2594.2594

Piguet, 1986, Administration of recombinant interleukin 2 to mice enhances production of hemopoietic and natural killer cells., Eur J Immunol., 16, 1257, 10.1002/eji.1830161012

Fehniger, 1997, Stem cell factor enhances interleukin-2-mediated expansion of murine natural killer cells in vivo., Blood., 90, 3647, 10.1182/blood.V90.9.3647

Caligiuri, 1993, Selective modulation of human natural killer cells in vivo after prolonged infusion of low dose recombinant interleukin 2., J Clin Invest., 91, 123, 10.1172/JCI116161

Bernstein, 1995, Prolonged administration of low-dose interleukin-2 in human immunodeficiency virus-associated malignancy results in selective expansion of innate immune effectors without significant clinical toxicity., Blood., 86, 3287, 10.1182/blood.V86.9.3287.bloodjournal8693287

Jacobson, 1996, Rational interleukin 2 therapy for HIV positive individuals: daily low doses enhance immune function without toxicity., Proc Natl Acad Sci U S A., 93, 10405, 10.1073/pnas.93.19.10405

Meropol, 1996, Daily subcutaneous injection of low-dose interleukin 2 expands natural killer cells in vivo without significant toxicity., Clin Cancer Res., 2, 669

Khatri, 1998, Ultra low dose interleukin-2 therapy promotes a type 1 cytokine profile in vivo in patients with AIDS and AIDS-associated malignancies., J Clin Invest., 101, 1373, 10.1172/JCI2038

Schorle, 1991, Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting., Nature., 352, 621, 10.1038/352621a0

Kundig, 1993, Immune responses in interleukin-2-deficient mice., Science., 262, 1059, 10.1126/science.8235625

DiSanto, 1995, Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain., Proc Natl Acad Sci U S A., 92, 377, 10.1073/pnas.92.2.377

Noguchi, 1993, Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans., Cell., 73, 147, 10.1016/0092-8674(93)90167-O

Suzuki, 1997, Abnormal development of intestinal intraepithelial lymphocytes and peripheral natural killer cells in mice lacking the IL-2 receptor beta chain., J Exp Med., 185, 499, 10.1084/jem.185.3.499

Lyman, 1998, c-kit ligand and Flt3 ligand: stem/progenitor cell factors with overlapping yet distinct activities., Blood., 91, 1101, 10.1182/blood.V91.4.1101

Yu, 1998, Flt3 ligand promotes the generation of a distinct CD34(+) human natural killer cell progenitor that responds to interleukin-15., Blood., 92, 3647, 10.1182/blood.V92.10.3647

Cavazzana-Calvo, 1996, Role of interleukin-2 (IL-2), IL-7, and IL-15 in natural killer cell differentiation from cord blood hematopoietic progenitor cells and from gamma c transduced severe combined immunodeficiency X1 bone marrow cells., Blood., 88, 3901, 10.1182/blood.V88.10.3901.bloodjournal88103901

Carayol, 1998, NK cells differentiated from bone marrow, cord blood and peripheral blood stem cells exhibit similar phenotype and functions., Eur J Immunol., 28, 1991, 10.1002/(SICI)1521-4141(199806)28:06<1991::AID-IMMU1991>3.0.CO;2-7

Jaleco, 1997, Fetal liver contains committed NK progenitors, but is not a site for development of CD34+ cells into T cells., J Immunol., 159, 694, 10.4049/jimmunol.159.2.694

Mingari, 1997, Interleukin-15-induced maturation of human natural killer cells from early thymic precursors: selective expression of CD94/NKG2-A as the only HLA class I-specific inhibitory receptor., Eur J Immunol., 27, 1374, 10.1002/eji.1830270612

Gaddy, 1997, Cord blood CD16+56− cells with low lytic activity are possible precursors of mature natural killer cells., Cell Immunol., 180, 132, 10.1006/cimm.1997.1175

Naora, 1999, Enhanced survival and potent expansion of the natural killer cell population of HIV-infected individuals by exogenous interleukin-15., Immunol Lett., 68, 359, 10.1016/S0165-2478(99)00077-2

Sanchez, 1994, Identification of a common T/natural killer cell progenitor in human fetal thymus., J Exp Med., 180, 569, 10.1084/jem.180.2.569

Williams, 1998, Natural killer cell differentiation: insights from knockout and transgenic mouse models and in vitro systems., Immunol Rev., 165, 47, 10.1111/j.1600-065X.1998.tb01229.x

Puzanov, 1996, IL-15 can substitute for the marrow microenvironment in the differentiation of natural killer cells., J Immunol., 157, 4282, 10.4049/jimmunol.157.10.4282

Williams, 1997, Generation of lytic natural killer 1.1+, Ly-49− cells from multipotential murine bone marrow progenitors in a stroma-free culture: definition of cytokine requirements and developmental intermediates., J Exp Med., 186, 1609, 10.1084/jem.186.9.1609

Williams, 1999, Differentiation of NK1.1+, Ly49+ NK cells from flt3+ multipotent marrow progenitor cells., J Immunol., 163, 2648, 10.4049/jimmunol.163.5.2648

Fujii, 1998, Functional dissection of the cytoplasmic subregions of the IL-2 receptor beta chain in primary lymphocyte populations., EMBO J., 17, 6551, 10.1093/emboj/17.22.6551

Cao, 1995, Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain., Immunity., 2, 223, 10.1016/1074-7613(95)90047-0

Park, 1995, Developmental defects of lymphoid cells in Jak3 kinase-deficient mice., Immunity., 3, 771, 10.1016/1074-7613(95)90066-7

Nosaka, 1995, Defective lymphoid development in mice lacking Jak3., Science., 270, 800, 10.1126/science.270.5237.800

Teglund, 1998, Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses., Cell., 93, 841, 10.1016/S0092-8674(00)81444-0

Imada, 1998, Stat5b is essential for natural killer cell-mediated proliferation and cytolytic activity., J Exp Med., 188, 2067, 10.1084/jem.188.11.2067

Barton, 1998, The Ets-1 transcription factor is required for the development of natural killer cells in mice., Immunity., 9, 555, 10.1016/S1074-7613(00)80638-X

Munger, 1995, Studies evaluating the antitumor activity and toxicity of interleukin-15, a new T cell growth factor: comparison with interleukin-2., Cell Immunol., 165, 289, 10.1006/cimm.1995.1216

Evans, 1997, IL-15 mediates anti-tumor effects after cyclophosphamide injection of tumor-bearing mice and enhances adoptive immunotherapy: the potential role of NK cell subpopulations., Cell Immunol., 179, 66, 10.1006/cimm.1997.1132

Kos, 1996, Immune regulation: a critical link between NK cells and CTLs., Immunol Today., 17, 174, 10.1016/0167-5699(96)80616-5

Flamand, 1996, Human herpesvirus-6 enhances natural killer cell cytotoxicity via IL-15., J Clin Invest., 97, 1373, 10.1172/JCI118557

Atedzoe, 1997, Enhancement of natural killer cell cytotoxicity by the human herpesvirus-7 via IL-15 induction., J Immunol., 159, 4966, 10.4049/jimmunol.159.10.4966

Ross, 1997, Cytokine-induced apoptosis of human natural killer cells identifies a novel mechanism to regulate the innate immune response., Blood., 89, 910, 10.1182/blood.V89.3.910

Fehniger, 1999, Costimulation of human natural killer cells is required for optimal interferon gamma (IFN-γ) production., Transplant Proc., 31, 1476, 10.1016/S0041-1345(99)00011-1

Fehniger, 1999, Differential cytokine and chemokine gene expression by human NK cells following activation with IL-18 or IL-15 in combination with IL-12: implications for the innate immune response., J Immunol., 162, 4511, 10.4049/jimmunol.162.8.4511

Fehniger, 2000, IL-15 costimulates the generalized Shwartzman reaction and innate immune IFN-γ production in vivo., J Immunol., 164, 1643, 10.4049/jimmunol.164.4.1643

Nishimura, 1996, IL-15 is a novel growth factor for murine gamma delta T cells induced by Salmonella infection., J Immunol., 156, 663, 10.4049/jimmunol.156.2.663

Mody, 1998, Interleukin-15 induces antimicrobial activity after release by Cryptococcus neoformans-stimulated monocytes., J Infect Dis., 178, 803, 10.1086/515381

Bluman, 1996, Human natural killer cells produce abundant macrophage inflammatory protein-1 alpha in response to monocyte-derived cytokines., J Clin Invest., 97, 2722, 10.1172/JCI118726

Fehniger, 1998, Natural killer cells from HIV-1+ patients produce C-C chemokines and inhibit HIV-1 infection., J Immunol., 161, 6433, 10.4049/jimmunol.161.11.6433

Maghazachi, 1994, C-C chemokines induce the chemotaxis of NK and IL-2-activated NK cells., J Immunol., 153, 4969, 10.4049/jimmunol.153.11.4969

Fahey, 1992, Macrophage inflammatory protein 1 modulates macrophage function., J Immunol., 148, 2764, 10.4049/jimmunol.148.9.2764

Liu, 1994, Granulated lymphoid cells of the pregnant uterus: morphological and functional features., Int Rev Cytol., 153, 105, 10.1016/S0074-7696(08)62189-0

King, 1991, CD3- leukocytes present in the human uterus during early placentation: phenotypic and morphological characterization of the CD56++ population., Dev Immunol., 1, 169, 10.1155/1991/83493

Nishikawa, 1991, Accumulation of CD16−CD56+ natural killer cells with high affinity interleukin 2 receptors in human early pregnancy decidua., Int Immunol., 3, 743, 10.1093/intimm/3.8.743

King, 1996, Human uterine natural killer cells., Nat Immun., 15, 41

Ye, 1996, The involvement of interleukin (IL)-15 in regulating the differentiation of granulated metrial gland cells in mouse pregnant uterus., J Exp Med., 184, 2405, 10.1084/jem.184.6.2405

Allen, 1998, Granzymes D, E, F, and G are regulated through pregnancy and by IL-2 and IL-15 in granulated metrial gland cells., J Immunol., 161, 2772, 10.4049/jimmunol.161.6.2772

Fortunato, 1998, IL-15, a novel cytokine produced by human fetal membranes, is elevated in preterm labor., Am J Reprod Immunol., 39, 16, 10.1111/j.1600-0897.1998.tb00328.x

Verma, 2000, Human decidual natural killer cells express the receptor for and respond to the cytokine interleukin 15., Biol Reprod., 62, 959, 10.1095/biolreprod62.4.959

Okada, 2000, Expression of interleukin-15 in human endometrium and decidua., Mol Hum Reprod., 6, 75, 10.1093/molehr/6.1.75

Espinoza-Delgado, 1990, Expression and role of p75 interleukin 2 receptor on human monocytes., J Exp Med., 171, 1821, 10.1084/jem.171.5.1821

Bosco, 1994, The gamma subunit of the interleukin-2 receptor is expressed in human monocytes and modulated by interleukin-2, interferon gamma, and transforming growth factor beta 1., Blood., 83, 3462, 10.1182/blood.V83.12.3462.3462

Alleva, 1997, IL-15 functions as a potent autocrine regulator of macrophage proinflammatory cytokine production: evidence for differential receptor subunit utilization associated with stimulation or inhibition., J Immunol., 159, 2941, 10.4049/jimmunol.159.6.2941

Djeu, 1993, Function associated with IL-2 receptor-beta on human neutrophils. Mechanism of activation of antifungal activity against Candida albicans by IL-2., J Immunol., 150, 960, 10.4049/jimmunol.150.3.960

Liu, 1994, Expression of interleukin-2 receptor γ chain on human neutrophils., Blood., 84, 3870, 10.1182/blood.V84.11.3870.bloodjournal84113870

Nakarai, 1994, Interleukin-2 receptor γ chain expression on resting and activated lymphoid cells., J Exp Med., 180, 241, 10.1084/jem.180.1.241

Musso, 1998, Interleukin-15 activates proinflammatory and antimicrobial functions in polymorphonuclear cells., Infect Immun., 66, 2640, 10.1128/IAI.66.6.2640-2647.1998

Girard, 1998, Human neutrophils express the interleukin-15 receptor alpha chain (IL-15Ralpha) but not the IL-9Ralpha component., Clin Immunol Immunopathol., 88, 232, 10.1006/clin.1998.4576

Girard, 1996, Differential effects of interleukin-15 (IL-15) and IL-2 on human neutrophils: modulation of phagocytosis, cytoskeleton rearrangement, gene expression, and apoptosis by IL-15., Blood., 88, 3176, 10.1182/blood.V88.8.3176.bloodjournal8883176

Allison, 1991, The immunobiology of T cells with invariant gamma delta antigen receptors., Annu Rev Immunol., 9, 679, 10.1146/annurev.iy.09.040191.003335

Tanaka, 1992, In utero treatment with monoclonal antibody to IL-2 receptor beta-chain completely abrogates development of Thy-1+ dendritic epidermal cells., Int Immunol., 4, 487, 10.1093/intimm/4.4.487

Schimpl, 1994, Development and function of the immune system in mice with targeted disruption of the interluekin-2 gene., Transgenesis and Targeted Mutagenesis in Immunology., 191, 10.1016/B978-0-12-105760-2.50017-0

Edelbaum, 1995, Interleukin (IL)-15 promotes the growth of murine epidermal gamma delta T cells by a mechanism involving the beta- and gamma c-chains of the IL- 2 receptor., J Invest Dermatol., 105, 837, 10.1111/1523-1747.ep12326630

Fujihashi, 1990, Regulatory function for murine intraepithelial lymphocytes. Two subsets of CD3+, T cell receptor-1+ intraepithelial lymphocyte T cells abrogate oral tolerance., J Immunol., 145, 2010, 10.4049/jimmunol.145.7.2010

Guy-Grand, 1993, Gut intraepithelial T lymphocytes., Curr Opin Immunol., 5, 247, 10.1016/0952-7915(93)90012-H

Poussier, 1994, Thymus independent T cell development and selection in the intestinal epithelium., Annu Rev Immunol., 12, 521, 10.1146/annurev.iy.12.040194.002513

Kawamoto, 1996, Rapid killing of murine lymph node T blasts by intestinal intraepithelial lymphocytes in vitro., Eur J Immunol., 26, 653, 10.1002/eji.1830260322

Rocha, 1995, Extrathymic T cell differentiation., Curr Opin Immunol., 7, 235, 10.1016/0952-7915(95)80008-5

Inagaki-Ohara, 1997, Interleukin-15 preferentially promotes the growth of intestinal intraepithelial lymphocytes bearing gamma delta T cell receptor in mice., Eur J Immunol., 27, 2885, 10.1002/eji.1830271121

Hirose, 1998, Interleukin-15 may be responsible for early activation of intestinal intraepithelial lymphocytes after oral infection with Listeria monocytogenes in rats., Infect Immun., 66, 5677, 10.1128/IAI.66.12.5677-5683.1998

Lai, 1999, IL-15 promotes survival but not effector function differentiation of CD8+ TCRalphabeta+ intestinal intraepithelial lymphocytes., J Immunol., 163, 5843, 10.4049/jimmunol.163.11.5843

Ebert, 1998, Interleukin 15 is a potent stimulant of intraepithelial lymphocytes., Gastroenterology., 115, 1439, 10.1016/S0016-5085(98)70022-8

Elloso, 1996, Human gamma delta T cell subset-proliferative response to malarial antigen in vitro depends on CD4+ T cells or cytokines that signal through components of the IL-2R., J Immunol., 157, 2096, 10.4049/jimmunol.157.5.2096

Garcia, 1998, IL-15 enhances the response of human gamma delta T cells to nonpeptide microbial antigens., J Immunol., 160, 4322, 10.4049/jimmunol.160.9.4322

Takano, 1998, Protective roles of gamma delta T cells and interleukin-15 in Escherichia coli infection in mice., Infect Immun., 66, 3270, 10.1128/IAI.66.7.3270-3278.1998

Bendelac, 1997, Mouse CD1-specific NK1 T cells: development, specificity, and function., Annu Rev Immunol., 15, 535, 10.1146/annurev.immunol.15.1.535

MacDonald, 1997, Development and function of natural killer 1+ T-cells., Biochem Soc Trans., 25, 696, 10.1042/bst0250696

Schmidt, 1986, A subset of natural killer cells in peripheral blood displays a mature T cell phenotype., J Exp Med., 164, 351, 10.1084/jem.164.1.351

Lanier, 1986, Human CD3+ T lymphocytes that express neither CD4 nor CD8 antigens., J Exp Med., 164, 339, 10.1084/jem.164.1.339

Dellabona, 1994, An invariant V alpha 24-J alpha Q/V beta 11 T cell receptor is expressed in all individuals by clonally expanded CD4−8− T cells., J Exp Med., 180, 1171, 10.1084/jem.180.3.1171

Ohteki, 1997, Role for IL-15/IL-15 receptor beta-chain in natural killer 1.1+ T cell receptor-alpha beta+ cell development., J Immunol., 159, 5931, 10.4049/jimmunol.159.12.5931

Boesteanu, 1997, Distinct roles for signals relayed through the common cytokine receptor gamma chain and interleukin 7 receptor alpha chain in natural T cell development., J Exp Med., 186, 331, 10.1084/jem.186.2.331

Kanegane, 1996, Activation of naive and memory T cells by interleukin-15., Blood., 88, 230, 10.1182/blood.V88.1.230.230

Ye, 1996, Interleukin-15 induces the expression of mRNAs of cytolytic mediators and augments cytotoxic activities in primary murine lymphocytes., Cell Immunol., 174, 54, 10.1006/cimm.1996.0293

Treiber-Held, 1996, IL-15 induces the release of soluble IL-2Ralpha from human peripheral blood mononuclear cells., Clin Immunol Immunopathol., 79, 71, 10.1006/clin.1996.0052

Bulfone-Paus, 1997, Differential regulation of human T lymphoblast functions by IL-2 and IL-15., Cytokine., 9, 507, 10.1006/cyto.1996.0194

Mingari, 1998, HLA class I-specific inhibitory receptors in human T lymphocytes: interleukin 15-induced expression of CD94/NKG2A in superantigen- or alloantigen-activated CD8+ T cells., Proc Natl Acad Sci U S A., 95, 1172, 10.1073/pnas.95.3.1172

Kumaki, 1996, Interleukin-15 up-regulates interleukin-2 receptor alpha chain but down-regulates its own high-affinity binding sites on human T and B cells., Eur J Immunol., 26, 1235, 10.1002/eji.1830260608

Bulfone-Paus, 1997, Interleukin-15 protects from lethal apoptosis in vivo., Nat Med., 3, 1124, 10.1038/nm1097-1124

Wilkinson, 1995, Chemoattraction of human blood T lymphocytes by interleukin-15., J Exp Med., 181, 1255, 10.1084/jem.181.3.1255

Perera, 1999, IL-15 induces the expression of chemokines and their receptors in T lymphocytes., J Immunol., 162, 2606, 10.4049/jimmunol.162.5.2606

Estess, 1999, Interleukin 15 induces endothelial hyaluronan expression in vitro and promotes activated T cell extravasation through a CD44-dependent pathway in vivo., J Exp Med., 190, 9, 10.1084/jem.190.1.9

Kuniyoshi, 1999, Dendritic cell secretion of IL-15 is induced by recombinant huCD40LT and augments the stimulation of antigen-specific cytolytic T cells., Cell Immunol., 193, 48, 10.1006/cimm.1999.1469

Avice, 1998, IL-15 promotes IL-12 production by human monocytes via T cell-dependent contact and may contribute to IL-12-mediated IFN-gamma secretion by CD4+ T cells in the absence of TCR ligation., J Immunol., 161, 3408, 10.4049/jimmunol.161.7.3408

Khan, 1996, IL-15 augments CD8+ T cell-mediated immunity against Toxoplasma gondii infection in mice., J Immunol., 157, 2103, 10.4049/jimmunol.157.5.2103

Seder, 1996, High-dose IL-2 and IL-15 enhance the in vitro priming of naive CD4+ T cells for IFN-gamma but have differential effects on priming for IL-4., J Immunol., 156, 2413, 10.4049/jimmunol.156.7.2413

Kim, 1998, Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens., Eur J Immunol., 28, 1089, 10.1002/(SICI)1521-4141(199803)28:03<1089::AID-IMMU1089>3.0.CO;2-L

Sin, 1999, In vivo modulation of vaccine-induced immune responses toward a Th1 phenotype increases potency and vaccine effectiveness in a herpes simplex virus type 2 mouse model., J Virol., 73, 501, 10.1128/JVI.73.1.501-509.1999

Xin, 1999, IL-15 expression plasmid enhances cell-mediated immunity induced by an HIV-1 DNA vaccine., Vaccine., 17, 858, 10.1016/S0264-410X(98)00271-0

Borger, 1999, Interleukin-15 differentially enhances the expression of interferon-gamma and interleukin-4 in activated human (CD4+) T lymphocytes., Immunology., 96, 207, 10.1046/j.1365-2567.1999.00679.x

Mori, 1996, IL-15 promotes cytokine production of human T helper cells., J Immunol., 156, 2400, 10.4049/jimmunol.156.7.2400

Ruckert, 1998, IL-15-IgG2b fusion protein accelerates and enhances a Th2 but not a Th1 immune response in vivo, while IL-2-IgG2b fusion protein inhibits both., Eur J Immunol., 28, 3312, 10.1002/(SICI)1521-4141(199810)28:10<3312::AID-IMMU3312>3.0.CO;2-I

Quinn, 1995, Interleukin-15: a novel anabolic cytokine for skeletal muscle., Endocrinology., 136, 3669, 10.1210/endo.136.8.7628408

Quinn, 1997, Interleukin-15 stimulates C2 skeletal myoblast differentiation., Biochem Biophys Res Commun., 239, 6, 10.1006/bbrc.1997.7414

Angiolillo, 1997, Interleukin-15 promotes angiogenesis in vivo., Biochem Biophys Res Commun., 233, 231, 10.1006/bbrc.1997.6435

Feldmann, 1996, Role of cytokines in rheumatoid arthritis., Annu Rev Immunol., 14, 397, 10.1146/annurev.immunol.14.1.397

McInnes, 1996, The role of interleukin-15 in T-cell migration and activation in rheumatoid arthritis., Nat Med., 2, 175, 10.1038/nm0296-175

McInnes, 1997, Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-alpha production in rheumatoid arthritis., Nat Med., 3, 189, 10.1038/nm0297-189

al-Mughales, 1996, The chemoattractant activity of rheumatoid synovial fluid for human lymphocytes is due to multiple cytokines., Clin Exp Immunol., 106, 230, 10.1046/j.1365-2249.1996.d01-836.x

Kotake, 1999, IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis., J Clin Invest., 103, 1345, 10.1172/JCI5703

Ziolkowska, 2000, High levels of IL-17 in rheumatoid arthritis patients: IL-15 triggers in vitro IL-17 production via cyclosporin A-sensitive mechanism., J Immunol., 164, 2832, 10.4049/jimmunol.164.5.2832

Gracie, 1999, A proinflammatory role for IL-18 in rheumatoid arthritis., J Clin Invest., 104, 1393, 10.1172/JCI7317

Thurkow, 1997, Increased expression of IL-15 in the synovium of patients with rheumatoid arthritis compared with patients with Yersinia-induced arthritis and osteoarthritis., J Pathol., 181, 444, 10.1002/(SICI)1096-9896(199704)181:4<444::AID-PATH778>3.0.CO;2-O

Ruchatz, 1998, Soluble IL-15 receptor alpha-chain administration prevents murine collagen-induced arthritis: a role for IL-15 in development of antigen-induced immunopathology., J Immunol., 160, 5654, 10.4049/jimmunol.160.11.5654

Agostini, 1998, Cytokines in sarcoidosis., Semin Respir Infect., 13, 184

Agostini, 1996, Role of IL-15, IL-2, and their receptors in the development of T cell alveolitis in pulmonary sarcoidosis., J Immunol., 157, 910, 10.4049/jimmunol.157.2.910

Ehrhardt, 1996, New insights into the immunopathology of chronic inflammatory bowel disease., Semin Gastrointest Dis., 7, 144

Kirman, 1996, Increased numbers of interleukin-15-expressing cells in active ulcerative colitis., Am J Gastroenterol., 91, 1789

Sakai, 1998, Interleukin 15 activity in the rectal mucosa of inflammatory bowel disease., Gastroenterology., 114, 1237, 10.1016/S0016-5085(98)70430-5

Liu, 2000, IL-15 is highly expressed in inflammatory bowel disease and regulates local T cell-dependent cytokine production., J Immunol., 164, 3608, 10.4049/jimmunol.164.7.3608

Kakumu, 1997, Serum levels of IL-10, IL-15 and soluble tumour necrosis factor-alpha (TNF-alpha) receptors in type C chronic liver disease., Clin Exp Immunol., 109, 458, 10.1046/j.1365-2249.1997.4861382.x

Kivisakk, 1998, IL-15 mRNA expression is up-regulated in blood and cerebrospinal fluid mononuclear cells in multiple sclerosis (MS)., Clin Exp Immunol., 111, 193, 10.1046/j.1365-2249.1998.00478.x

Pashenkov, 1999, Levels of interleukin-15-expressing blood mononuclear cells are elevated in multiple sclerosis., Scand J Immunol., 50, 302, 10.1046/j.1365-3083.1999.00598.x

Steinman, 1996, Multiple sclerosis: a coordinated immunological attack against myelin in the central nervous system., Cell., 85, 299, 10.1016/S0092-8674(00)81107-1

Means-Markwell, 2000, Eosinophilia with aberrant T cells and elevated serum levels of interleukin-2 and interleukin-15., N Engl J Med., 342, 1568, 10.1056/NEJM200005253422104

VanBuskirk, 1997, Transplantation immunology., JAMA., 278, 1993, 10.1001/jama.1997.03550220199025

Pavlakis, 1996, Intragraft IL-15 transcripts are increased in human renal allograft rejection., Transplantation., 62, 543, 10.1097/00007890-199608270-00020

Baan, 1998, Increased intragraft IL-15 mRNA expression after liver transplantation., Clin Transplant., 12, 212

van Gelder, 1998, Blockade of the interleukin (IL)-2/IL-2 receptor pathway with a monoclonal anti-IL-2 receptor antibody (BT563) does not prevent the development of acute heart allograft rejection in humans., Transplantation., 65, 405, 10.1097/00007890-199802150-00020

Baan, 1999, Anti-CD25 therapy reveals the redundancy of the intragraft cytokine network after clinical heart transplantation., Transplantation., 67, 870, 10.1097/00007890-199903270-00014

Li, 1998, IL-2 and IL-4 double knockout mice reject islet allografts: a role for novel T cell growth factors in allograft rejection., J Immunol., 161, 890, 10.4049/jimmunol.161.2.890

Maeda, 1987, Evidence for the interleukin-2 dependent expansion of leukemic cells in adult T cell leukemia., Blood., 70, 1407, 10.1182/blood.V70.5.1407.1407

Yodoi, 1987, Interleukin-2 receptor-inducing factor(s) in adult T cell leukemia., Acta Haematol., 78, 56, 10.1159/000205904

Yamada, 1998, Interleukin-15 (IL-15) can replace the IL-2 signal in IL-2-dependent adult T-cell leukemia (ATL) cell lines: expression of IL-15 receptor alpha on ATL cells., Blood., 91, 4265, 10.1182/blood.V91.11.4265

Xu, 1995, Constitutive activation of different Jak tyrosine kinases in human T cell leukemia virus type 1 (HTLV-1) tax protein or virus-transformed cells., J Clin Invest., 96, 1548, 10.1172/JCI118193

Takemoto, 1997, Proliferation of adult T cell leukemia/lymphoma cells is associated with the constitutive activation of JAK/STAT proteins., Proc Natl Acad Sci U S A., 94, 13897, 10.1073/pnas.94.25.13897

Burg, 1995, Pathology of cutaneous T-cell lymphoma., Hematol Oncol Clin North Am., 9, 961, 10.1016/S0889-8588(18)30053-4

Dalloul, 1992, Interleukin-7 is a growth factor for Sezary lymphoma cells., J Clin Invest., 90, 1054, 10.1172/JCI115920

Foss, 1994, Costimulation of cutaneous T-cell lymphoma cells by interleukin-7 and interleukin-2: potential autocrine or paracrine effectors in the Sezary syndrome., J Clin Oncol., 12, 326, 10.1200/JCO.1994.12.2.326

LeMaistre, 1998, Phase I trial of a ligand fusion-protein (DAB389IL-2) in lymphomas expressing the receptor for interleukin-2., Blood., 91, 399

Dobbeling, 1998, Interleukin-15 is an autocrine/paracrine viability factor for cutaneous T-cell lymphoma cells., Blood., 92, 252, 10.1182/blood.V92.1.252.413k08_252_258

Qin, 1999, Constitutive and interleukin-7/interleukin-15 stimulated DNA binding of myc, jun, and novel myc-like proteins in cutaneous T-cell lymphoma cells., Blood., 93, 260, 10.1182/blood.V93.1.260

Bazarbachi, 1994, HTLV-1-like particles and HTLV-1-related DNA sequences in an unambiguous case of Sezary syndrome., Leukemia., 8, 201

Rich, 1993, Cutaneous lymphoproliferation and lymphomas in interleukin 7 transgenic mice., J Exp Med., 177, 305, 10.1084/jem.177.2.305

Ishida, 1989, Effects of the deregulated expression of human interleukin-2 in transgenic mice., Int Immunol., 1, 113, 10.1093/intimm/1.2.113

Zambello, 1998, Large granular lymphocytosis., Haematologica., 83, 936

Zambello, 1997, Interleukin-15 triggers the proliferation and cytotoxicity of granular lymphocytes in patients with lymphoproliferative disease of granular lymphocytes., Blood., 89, 201, 10.1182/blood.V89.1.201

Natkunam, 1999, Aggressive natural killer-like T-cell malignancy with leukemic presentation following solid organ transplantation., Am J Clin Pathol., 111, 663, 10.1093/ajcp/111.5.663

Natkunam, 1999, Aggressive cutaneous NK and NK-like T-cell lymphomas: clinicopathologic, immunohistochemical, and molecular analyses of 12 cases., Am J Surg Pathol., 23, 571, 10.1097/00000478-199905000-00012

Armitage, 1995, IL-15 has stimulatory activity for the induction of B cell proliferation and differentiation., J Immunol., 154, 483, 10.4049/jimmunol.154.2.483

Trentin, 1996, Interleukin-15 promotes the growth of leukemic cells of patients with B-cell chronic lymphoproliferative disorders., Blood., 87, 3327, 10.1182/blood.V87.8.3327.bloodjournal8783327

Meazza, 1998, Interleukin (IL)-15 induces survival and proliferation of the growth factor-dependent acute myeloid leukemia M-07e through the IL-2 receptor beta/gamma., Int J Cancer., 78, 189, 10.1002/(SICI)1097-0215(19981005)78:2<189::AID-IJC12>3.0.CO;2-6

Tinhofer, 2000, Expression of functional interleukin-15 receptor and autocrine production of interleukin-15 as mechanisms of tumor propagation in multiple myeloma., Blood., 95, 610, 10.1182/blood.V95.2.610

Lollini, 1997, Expression of interleukin 15 (IL-15) in human rhabdomyosarcoma, osteosarcoma and Ewing's sarcoma., Int J Cancer., 71, 732, 10.1002/(SICI)1097-0215(19970529)71:5<732::AID-IJC7>3.0.CO;2-S

Barzegar, 1998, IL-15 is produced by a subset of human melanomas, and is involved in the regulation of markers of melanoma progression through juxtacrine loops., Oncogene., 16, 2503, 10.1038/sj.onc.1201775

Trinder, 1999, Constitutive and IFN-gamma regulated expression of IL-7 and IL-15 in human renal cell cancer., Int J Oncol., 14, 23

Seder, 1995, Cytokine interactions in human immunodeficiency virus-infected individuals: roles of interleukin (IL)-2, IL-12, and IL-15., J Exp Med., 182, 1067, 10.1084/jem.182.4.1067

Patki, 1996, Activation of antigen-induced lymphocyte proliferation by interleukin-15 without the mitogenic effect of interleukin-2 that may induce human immunodeficiency virus-1 expression., J Clin Invest., 98, 616, 10.1172/JCI118831

Kanai, 1996, IL-15 stimulates the expansion of AIDS virus-specific CTL., J Immunol., 157, 3681, 10.4049/jimmunol.157.8.3681

Lucey, 1997, In vitro immunologic and virologic effects of interleukin 15 on peripheral blood mononuclear cells from normal donors and human immunodeficiency virus type 1-infected patients., Clin Diagn Lab Immunol., 4, 43, 10.1128/CDLI.4.1.43-48.1997

Chehimi, 1997, IL-15 enhances immune functions during HIV infection., J Immunol., 158, 5978, 10.4049/jimmunol.158.12.5978

Agostini, 1997, Interleukin-15 triggers activation and growth of the CD8 T-cell pool in extravascular tissues of patients with acquired immunodeficiency syndrome., Blood., 90, 1115, 10.1182/blood.V90.3.1115

Agostini, 1999, CD8 T-cell infiltration in extravascular tissues of patients with human immunodeficiency virus infection. Interleukin-15 upmodulates costimulatory pathways involved in the antigen-presenting cells-T-cell interaction., Blood., 93, 1277, 10.1182/blood.V93.4.1277

Bayard-McNeeley, 1996, Differential effects of interleukin-12, interleukin-15, and interleukin-2 on human immunodeficiency virus type 1 replication in vitro., Clin Diagn Lab Immunol., 3, 547, 10.1128/CDLI.3.5.547-553.1996

Al-Harthi, 1998, Induction of HIV-1 replication by type 1-like cytokines, interleukin (IL)-12 and IL-15: effect on viral transcriptional activation, cellular proliferation, and endogenous cytokine production., J Clin Immunol., 18, 124, 10.1023/A:1023246800353

Lin, 1997, Human immunodeficiency virus (HIV) type-1 GP120-specific cell-mediated cytotoxicity (CMC) and natural killer (NK) activity in HIV-infected (HIV+) subjects: enhancement with interleukin-2 (IL-2), IL-12, and IL-15., Clin Immunol Immunopathol., 82, 163, 10.1006/clin.1996.4298

Azimi, 1999, Involvement of IL-15 in the pathogenesis of human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis: implications for therapy with a monoclonal antibody directed to the IL-2/15Rbeta receptor., J Immunol., 163, 4064, 10.4049/jimmunol.163.7.4064

Gosselin, 1999, Interleukin-15 as an activator of natural killer cell-mediated antiviral response., Blood., 94, 4210, 10.1182/blood.V94.12.4210

Lauw, 1999, Elevated plasma concentrations of interferon (IFN)-gamma and the IFN-gamma-inducing cytokines interleukin (IL)-18, IL-12, and IL-15 in severe melioidosis., J Infect Dis., 180, 1878, 10.1086/315155

Elloso, 1998, The effects of interleukin-15 on human gammadelta T cell responses to Plasmodium falciparum in vitro., Immunol Lett., 64, 125, 10.1016/S0165-2478(98)00088-1

Carson, 1999, A fatal cytokine-induced systemic inflammatory response reveals a critical role for NK cells., J Immunol., 162, 4943, 10.4049/jimmunol.162.8.4943

Billiau, 1988, Gamma-interferon: the match that lights the fire?, Immunol Today., 9, 37, 10.1016/0167-5699(88)91256-X

Brozna, 1990, Shwartzman reaction., Semin Thromb Hemost., 16, 326, 10.1055/s-2007-1002685

Ozmen, 1994, Interleukin 12, interferon gamma, and tumor necrosis factor alpha are the key cytokines of the generalized Shwartzman reaction., J Exp Med., 180, 907, 10.1084/jem.180.3.907

Wysocka, 1995, Interleukin-12 is required for interferon-gamma production and lethality in lipopolysaccharide-induced shock in mice., Eur J Immunol., 25, 672, 10.1002/eji.1830250307

Movat, 1987, Acute inflammation and a Shwartzman-like reaction induced by interleukin-1 and tumor necrosis factor. Synergistic action of the cytokines in the induction of inflammation and microvascular injury., Am J Pathol., 129, 463

Moore, 1999, Adjuvant therapy of colon cancer., Semin Oncol., 26, 545

Cao, 1998, Interleukin 15 protects against toxicity and potentiates antitumor activity of 5-fluorouracil alone and in combination with leucovorin in rats bearing colorectal cancer., Cancer Res., 58, 1695

Cao, 1998, Interleukin 15 offers selective protection from irinotecan-induced intestinal toxicity in a preclinical animal model., Cancer Res., 58, 3270

Kaushansky, 2000, Blood: new designs for a new millennium., Blood., 95, 1, 10.1182/blood.V95.1.1

Kobayashi, 1999, Differences in pharmacokinetics and biodistribution between interleukin-2 and interleukin-15., FASEB J., 13, A1143

Moreland, 1997, Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein., N Engl J Med., 337, 141, 10.1056/NEJM199707173370301

Garrison, 1999, Etanercept: therapeutic use in patients with rheumatoid arthritis., Ann Rheum Dis., 58, I65, 10.1136/ard.58.2008.i65

Kim, 1998, Targeting the IL-15 receptor with an antagonist IL-15 mutant/Fc gamma2a protein blocks delayed-type hypersensitivity., J Immunol., 160, 5742, 10.4049/jimmunol.160.12.5742

McInnes, 1998, Interleukin 15: a proinflammatory role in rheumatoid arthritis synovitis., Immunol Today., 19, 75, 10.1016/S0167-5699(97)01205-X

Bazan, 1992, Unraveling the structure of IL-2., Science., 257, 410, 10.1126/science.1631562

McKenna, 1996, Targeted disruption of the flt3 ligand gene in mice affects multiple hematopoietic lineages, including natural killer cells, B lymphocytes, and dendritic cells., Blood., 88, 474a

Colucci, 2000, The receptor tyrosine kinase c-kit provides a critical signal for survival, expansion, and maturation of mouse natural killer cells., Blood., 95, 984, 10.1182/blood.V95.3.984.003k40_984_991