Altered T cell signalling in ageing

Mechanisms of Ageing and Development - Tập 122 Số 14 - Trang 1613-1637 - 2001
Graham Pawelec1, Katsuiku Hirokawa2, Tamàs Fülöp3
1University of Tübingen, Tübingen, Germany
2Department of Pathology and Immunology, Aging and Developmental Sciences, Tokyo Medical and Dental University Graduate School, Tokyo, Japan
3Institut Universitaire de Geriatrie, Sherbrooke, Quebec, Canada

Tóm tắt

Từ khóa


Tài liệu tham khảo

Adibzadeh, 1995, Long-term culture of monoclonal human T lymphocytes: models for immunosenescence?, Mech. Ageing Dev., 83, 171, 10.1016/0047-6374(95)01625-A

Akiba, 1999, CD28-independent costimulation of T cells by OX40 ligand and CD70 on activated B cells, J. Immunol., 162, 7058, 10.4049/jimmunol.162.12.7058

Altman, 2000, Protein kinase C theta: a new essential superstar on the T-cell stage, Immunol. Today, 21, 567, 10.1016/S0167-5699(00)01749-7

Arlinger, 1999, Interleukin/interferon signaling—a 1999 perspective, Immunologist, 7, 139

Becker, 2000, Differential expression of CD28 and CD94/NKG2 on T cells with identical TCR beta variable regions in primary melanoma and sentinel lymph node, Eur. J. Immunol., 30, 3699, 10.1002/1521-4141(200012)30:12<3699::AID-IMMU3699>3.0.CO;2-2

Beier, 2000, Induction, binding specificity and function of human ICOS, Eur. J. Immunol., 30, 3707, 10.1002/1521-4141(200012)30:12<3707::AID-IMMU3707>3.0.CO;2-Q

Bernstein, 1998, Effect of age on cytokine production in humans, Age, 21, 137, 10.1007/s11357-998-0024-6

Bining, 1997, Cytokine production by subsets of CD4 memory T cells differing in P-glycoprotein expression: Effects of aging, J. Gerontol. Ser. A—Biol. Sci. Med., 52, B137, 10.1093/gerona/52A.3.B137

Boucher, 1998, CD28 expression in T cell aging and human longevity, Exp. Gerontol., 33, 267, 10.1016/S0531-5565(97)00132-0

Boussiotis, 1997, Induction of T cell clonal anergy results in resistance, whereas CD28-mediated costimulation primes for susceptibility to Fas- and Bax-mediated programmed cell death, J. Immunol., 159, 3156, 10.4049/jimmunol.159.7.3156

Buonfiglio, 2000, The T cell activation molecule H4 and the CD28-like molecule ICOS are identical, Eur. J. Immunol., 30, 3463, 10.1002/1521-4141(2000012)30:12<3463::AID-IMMU3463>3.0.CO;2-5

Chambers, 1997, Co-stimulation in T cell responses, Curr. Opin. Immunol., 9, 396, 10.1016/S0952-7915(97)80087-8

Chopra, 1989, Interleukin 2, interleukin 2 receptor, and interferon-gamma synthesis and mRNA expression in phorbol myristate acetate and calcium ionophore A23187-stimulated T cells from elderly humans, Clin. Immunol. Immunopathol., 53, 297, 10.1016/0090-1229(89)90058-5

Coles, 2000, Memory CD8 T lymphocytes express inhibitory MHC-specific Ly49 receptors, Eur. J. Immunol., 30, 236, 10.1002/1521-4141(200001)30:1<236::AID-IMMU236>3.0.CO;2-X

Conconi, 1997, Proteasome inactivation upon aging and on oxidation-effect of HSP 90, Mol. Biol. Rep., 24, 45, 10.1023/A:1006852506884

Coyle, 2000, The CD28-related molecule ICOS is required for effective T cell-dependent immune responses, Immunity, 13, 95, 10.1016/S1074-7613(00)00011-X

De Benedette, 1999, Analysis of 4-1BB ligand (4-1BBL)-deficient mice and of mice lacking both 4-1BBL and CD28 reveals a role for 4-1BBL in skin allograft rejection and in the cytotoxic T cell response to influenza virus, J. Immunol., 163, 4833, 10.4049/jimmunol.163.9.4833

Di Pietro, 1998, Age-related defect of phospholipase C activity, differential expression of the beta(2) isoform in active T lymphocytes from aged humans, Hum. Immunol., 59, 25, 10.1016/S0198-8859(97)00228-0

Di Pietro, 2000, Age-dependent variations in the expression of PLC isoforms upon mitogenic stimulation of peripheral blood T cells from healthy donors, Br. J. Haematol., 111, 1209

Dobber, 1994, Mel14(+) CD4(+) T cells from aged mice display functional and phenotypic characteristics of memory cells, Int. Immunol., 6, 1227, 10.1093/intimm/6.8.1227

Douek, 1998, Changes in thymic function with age and during the treatment of HIV infection, Nature, 396, 690, 10.1038/25374

Dustin, 2000, The immunological synapse and the actin cytoskeleton: molecular hardware for T cell signaling, Nat. Immunol., 1, 23, 10.1038/76877

Effros, 1994, Decline in CD28(+) T cells in centenarians and in long-term T cell cultures: A possible cause for both in vivo and in vitro immunosenescence, Exp. Gerontol., 29, 601, 10.1016/0531-5565(94)90073-6

Eisenbraun, 2000, Altered composition of the immunological synapse in an anergic, age-dependent memory T cell subset, J. Immunol., 164, 6105, 10.4049/jimmunol.164.12.6105

Engwerda, 1994, Aged T cells are hyporesponsive to costimulation mediated by CD28, J. Immunol., 152, 3740, 10.4049/jimmunol.152.8.3740

Engwerda, 1996, An age-related decrease in rescue from T cell death following costimulation mediated by CD28, Cell Immunol., 170, 141, 10.1006/cimm.1996.0144

Enioutina, 2000, Enhancement of common mucosal immunity in aged mice following their supplementation with various antioxidants, Vaccine, 18, 2381, 10.1016/S0264-410X(00)00008-6

Faasen, 1989, Diminished heat shock protein synthesis following mitogen stimulation of lymphocytes from aged donors, Exp. Cell. Res., 183, 326, 10.1016/0014-4827(89)90393-5

Fagnoni, 1996, Expansion of cytotoxic CD8(+) CD28(−) T cells in healthy ageing people, including centenarians, Immunology, 88, 501, 10.1046/j.1365-2567.1996.d01-689.x

Fernandez-Gutierrez, 1999, Early lymphocyte activation in elderly humans: Impaired T and T-dependent B cell responses, Exp. Gerontol., 34, 217, 10.1016/S0531-5565(98)00068-0

Fiorentini, 1999, Generation of CD28(−) cells from long-term-stimulated CD8(+)CD28(+) T cells: a possible mechanism accounting for the increased number of CD8(+)CD28(−) T cells in HIV-1-infected patients, J. Leukocyte Biol., 65, 641, 10.1002/jlb.65.5.641

Fischer, 1999, Function and dysfunction of CD4(+) T cells in the immune response to melanoma, Cancer Immunol. Immunother., 48, 363, 10.1007/s002620050587

Freeman, 2000, Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation, J. Exp. Med., 192, 1027, 10.1084/jem.192.7.1027

Froelich, 1988, Phytohemagglutinin-induced proliferation by aged lymphocytes: reduced expression of high affinity interleukin 2 receptors and interleukin 2 secretion, Life Sci., 43, 1583, 10.1016/0024-3205(88)90529-2

Fülöp, 1993, Age-dependent changes in transmembrane signalling -identification of G-proteins in human lymphocytes and polymorphonuclear leukocytes, Cell Signal., 5, 593, 10.1016/0898-6568(93)90054-P

Fülöp, 1995, Cellular distribution of protein kinase C isozymes in CD3-mediated stimulation of human T lymphocytes with aging, FEBS Lett., 375, 69, 10.1016/0014-5793(95)01179-I

Fülöp, 1999, Age-related impairment of p56(Lck) and ZAP-70 activities in human T lymphocytes activated through the TcR/CD3 complex, Exp. Gerontol., 34, 197, 10.1016/S0531-5565(98)00061-8

Fülöp, T., Douziech, N., Goulet, A.C., Desgeorges, S., Linteau, A., Lacombe, G., Dupuis, G., 2001. Cyclodextrin modulation of T lymphocyte signal transduction with aging, Mech. Ageing Dev. (in press).

Gaglia, 2000, Intercellular adhesion molecule 1 is critical for activation of CD28-deficient T cells, J. Immunol., 165, 6091, 10.4049/jimmunol.165.11.6091

Garcia, 1997, Differential tyrosine phosphorylation of zeta chain dimers in mouse CD4 T lymphocytes: Effect of age, Cell Immunol., 175, 51, 10.1006/cimm.1996.1040

Garcia, 1998, Increased Zap-70 association with CD3 zeta in CD4 T cells from old mice, Cell Immunol., 190, 91, 10.1006/cimm.1998.1394

Garcia, 2001, Single-cell analyses reveal two defects in peptide-specific activation of naive T cells from aged mice, J. Immunol., 166, 3151, 10.4049/jimmunol.166.5.3151

Geginat, 2000, CD28 and LFA-1 contribute to cyclosporin A-resistant T cell growth by stabilizing the IL-2 mRNA through distinct signaling pathways, Eur. J. Immunol., 30, 1136, 10.1002/(SICI)1521-4141(200004)30:4<1136::AID-IMMU1136>3.0.CO;2-3

Gesbert, 1998, Recent advances in the understanding of interleukin-2 signal transduction, J. Clin. Immunol., 18, 307, 10.1023/A:1023223614407

Ginaldi, 2000, Immunophenotypical changes of T lymphocytes in the elderly, Gerontology, 46, 242, 10.1159/000022167

Godfrey, 1994, Identification of a human OX-40 ligand, a costimulator of CD4+ T cells with homology to tumor necrosis factor, J. Exp. Med., 180, 757, 10.1084/jem.180.2.757

Gorgas, 1997, Diminished activation of the MAP kinase pathway in CD3-stimulated T lymphocytes from old mice, Mech. Ageing Dev., 94, 71, 10.1016/S0047-6374(96)01857-X

Gramaglia, 2000, The OX40 costimulatory receptor determines the development of CD4 memory by regulating primary clonal expansion, J. Immunol., 165, 3043, 10.4049/jimmunol.165.6.3043

Granelli-Piperno, 1990, The effect of immunosuppressive agents on the induction of nuclear factors that bind to sites on the interleukin 2 promoter, J. Exp. Med., 172, 1869, 10.1084/jem.172.6.1869

Guerra, 2000, Killer inhibitory receptor (CD158b) modulates the lytic activity of tumor-specific T lymphocytes infiltrating renal cell carcinomas, Blood, 95, 2883, 10.1182/blood.V95.9.2883.009k22_2883_2889

Guidi, 1998, Changes in the amount and level of phosphorylation of p56lck in PBL from aging humans, Mech. Ageing Dev., 102, 177, 10.1016/S0047-6374(97)00144-9

Hara, 1988, Age-related changes of expression of IL-2 receptor subunits and kinetics of IL-2 internalization in T cells after mitogenic stimulation, Mech. Ageing Dev., 45, 167, 10.1016/0047-6374(88)90106-6

Haynes, 1999, Interleukin 2, but not other common gamma chain-binding cytokines, can reverse the defect in generation of CD4 effector T cells from naive T cells of aged mice, J. Exp. Med., 190, 1013, 10.1084/jem.190.7.1013

Hoshino, 1993, Tissue-specific distribution and age-dependent increase of human CD11b+ T-cells, J. Immunol., 151, 2237, 10.4049/jimmunol.151.4.2237

Hutloff, 1999, ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28, Nature, 397, 263, 10.1038/16717

Jackola, 1995, Diminished cell-cell binding by lymphocytes from healthy, elderly humans: Evidence for altered activation of LFA-1 function with age, J. Gerontol. Ser. A—Biol. Sci. Med., 50, B368, 10.1093/gerona/50A.6.B368

Keller, 2000, Possible involvement of proteasome inhibition in aging: implications for oxidative stress, Mech. Ageing Dev., 113, 61, 10.1016/S0047-6374(99)00101-3

Kirchhoff, 2000, TCR-mediated up-regulation of c-FLIPshort correlates with resistance toward CD95-mediated apoptosis by blocking death-inducing signaling complex activity, J. Immunol., 165, 6293, 10.4049/jimmunol.165.11.6293

Kirchhoff, 2000, Up-regulation of c-FLIPshort and reduction of activation-induced cell death in CD28-co-stimulated human T cells, Eur. J. Immunol., 30, 2765, 10.1002/1521-4141(200010)30:10<2765::AID-IMMU2765>3.0.CO;2-W

Kirk, 1998, Analysis of Raf-1 activation in response to TCR activation and costimulation in murine T-lymphocytes: Effect of age, Cell Immunol., 190, 33, 10.1006/cimm.1998.1382

Kirk, 1999, Age-sensitive and -insensitive pathways leading to JNK activation in mouse CD4(+) T-cells, Cell Immunol., 197, 83, 10.1006/cimm.1999.1568

Kirk, 1999, Age-related decline in activation of JNK by TCR- and CD28-mediated signals in murine T-lymphocytes, Cell Immunol., 197, 75, 10.1006/cimm.1999.1567

Kunitomi, 2000, Vascular endothelial cells provide T cells with costimulatory signals via the OX40/gp34 system, J. Leukocyte Biol., 68, 111, 10.1189/jlb.68.1.111

Kurashima, 1997, Age-related changes of cytokine production by murine helper T cell subpopulations, Pathobiology, 65, 155, 10.1159/000164117

Kurt, 2000, TCR V-beta usage and clonality of T cells isolated from progressing and rejected tumor sites before and after in vitro culture, Int. Immunol., 12, 639, 10.1093/intimm/12.5.639

Labalette, 1999, Peripheral human CD8(+)CD28(+) T lymphocytes give rise to CD28(−) progeny, but IL-4 prevents loss of CD28 expression, Int. Immunol., 11, 1327, 10.1093/intimm/11.8.1327

Leupin, 2000, Exclusion of CD45 from the T-cell receptor signaling area in antigen-stimulated T lymphocytes, Curr. Biol., 10, 277, 10.1016/S0960-9822(00)00362-6

Li, 2000, Impaired signal transduction in mitogen activated rat splenic lymphocytes during aging, Mech. Ageing Dev., 113, 85, 10.1016/S0047-6374(99)00096-2

Lin, 2001, T cell receptor signalling, J. Cell. Sci., 114, 243, 10.1242/jcs.114.2.243

Linton, 1996, Antigen-independent changes in naive CD4 T cells with aging, J. Exp. Med., 184, 1891, 10.1084/jem.184.5.1891

Lio, 1998, Interleukin 12-release by mitogen-stimulated mononuclear cells in the elderly, Mech. Ageing Dev., 102, 211, 10.1016/S0047-6374(98)00016-5

Liu, 1997, Reductions in the activation of ERK and JNK are associated with decreased IL-2 production in T cells from elderly humans stimulated by the TCR/CD3 complex and costimulatory signals, Cell Immunol., 182, 79, 10.1006/cimm.1997.1226

Livak, 1996, T-cell receptor alpha locus V(D)J recombination by-products are abundant in thymocytes and mature T cells, Mol. Cell. Biol., 16, 609, 10.1128/MCB.16.2.609

Marelli-Berg, 1999, Recently activated T cells are costimulation-dependent in vitro, Cell Immunol., 195, 18, 10.1006/cimm.1999.1521

Marti, 2001, Negative-feedback regulation of CD28 costimulation by a novel mitogen-activated protein kinase phosphatase, MKP6, J. Immunol., 166, 197, 10.4049/jimmunol.166.1.197

Mattila, 1990, The actions of cyclosporin A and FK506 suggest a novel step in the activation of T lymphocytes, EMBO J., 9, 4425, 10.1002/j.1460-2075.1990.tb07893.x

McFarland, 2000, Identification of a human recent thymic emigrant phenotype, Proc. Natl. Acad. Sci. USA, 97, 4215, 10.1073/pnas.070061597

Miller, 1987, Diminished calcium influx in lectin-stimulated T cells from old mice, J. Cell. Physiol., 132, 337, 10.1002/jcp.1041320220

Miller, 1994, Lack of B7-2 expression in the germinal centers of aged mice, Aging: Immunol. Infect. Dis., 5, 249

Minami, 1993, Association of p56(lck) with IL-2 receptor beta-chain is critical for the IL-2-induced activation of p56(lck), EMBO J., 12, 759, 10.1002/j.1460-2075.1993.tb05710.x

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

Nam, 1998, Age-dependent remodeling of peripheral blood CD4(+) CD8(+) T lymphocytes in Cynomolgus monkeys, Dev. Comp. Immunol., 22, 239, 10.1016/S0145-305X(97)00058-X

Namekawa, 2000, Killer cell activating receptors function as costimulatory molecules on CD4(+)CD28(Null) T cells clonally expanded in rheumatoid arthritis, J. Immunol., 165, 1138, 10.4049/jimmunol.165.2.1138

Northrop, 1994, NF-AT components define a family of transcription factors targeted in T-cell activation, Nature, 369, 497, 10.1038/369497a0

O'Leary, 1988, Expression of the human T cell antigen receptor complex in advanced age, Mech. Ageing Dev., 45, 239, 10.1016/0047-6374(88)90006-1

Pahlavani, 1996, The age-related changes in DNA binding activity of AP-1, NF-kappa B, and OCT-1 transcription factors in lymphocytes from rats, Age, 19, 45, 10.1007/BF02434070

Pahlavani, 1999, Age-related decline in activation of calcium/calmodulin-dependent phosphatase calcineurin and kinase CaMK-IV in rat T cells, Mech. Ageing Dev., 112, 59, 10.1016/S0047-6374(99)00077-9

Pahlavani, 1995, The age-related decline in the induction of IL-2 transcription is correlated to changes in the transcription factor NFAT, Cell. Immunol., 165, 84, 10.1006/cimm.1995.1190

Pahlavani, 1998, Activation of p21(ras)/MAPK signal transduction molecules decreases with age in mitogen-stimulated T cells from rats, Cell Immunol., 185, 39, 10.1006/cimm.1998.1274

Pawelec, 1996, Interleukin 10 protects activated human T lymphocytes against growth factor withdrawal-induced cell death but only anti-fas antibody can prevent activation-induced cell death, Cytokine, 8, 877, 10.1006/cyto.1996.0117

Pawelec, 1997, Human T cell clones as a model for immunosenescence, Immunol. Rev., 160, 31, 10.1111/j.1600-065X.1997.tb01025.x

Pawelec, 1998, Extrathymic T cell differentiation in vitro from human CD34(+) stem cells, J. Leukocyte Biol., 64, 733, 10.1002/jlb.64.6.733

Pawelec, 2000, Longevity in vitro of human CD4+ T helper cell clones derived from young donors and elderly donors, or from progenitor cells: age-associated differences in cell surface molecule expression and cytokine secretion, Biogerontology, 1, 247, 10.1023/A:1010086229931

Ponnappan, 1999, Decreased proteasome-mediated degradation in T cells from the elderly: A role in immune senescence, Cell Immunol., 192, 167, 10.1006/cimm.1998.1418

Potestio, 1999, Age-related changes in the expression of CD95 (APO1/FAS) on blood lymphocytes, Exp. Gerontol., 34, 659, 10.1016/S0531-5565(99)00041-8

Poynter, 1998, Peroxisome proliferator-activated receptor alpha activation modulates cellular redox status, represses nuclear factor-kappa B signaling, and reduced inflammatory cytokine production in aging, J. Biol. Chem., 273, 32833, 10.1074/jbc.273.49.32833

Pucci, 1998, Inhibition of IL-2 production by Nil-2-a in murine T cells, Int. Immunol., 10, 1435, 10.1093/intimm/10.10.1435

Quadri, 1996, Age-related tyrosine-specific protein phosphorylation defect in human T lymphocytes activated through CD3, CD4, CD8 or the IL-2 receptor, Mech. Ageing Dev., 88, 125, 10.1016/0047-6374(96)01715-0

Russ, 1998, P-glycoprotein plays an insignificant role in the presentation of antigenic peptides to CD8+ T cells, Cancer Res., 58, 4688

Russell, 1995, Mutation of Jak3 in a patient with SCID: Essential role of Jak3 in lymphoid development, Science, 270, 797, 10.1126/science.270.5237.797

Salkind, 1994, Influence of age on the production of Fos and Jun by influenza virus-exposed T cells, J. Leukocyte Biol., 56, 817, 10.1002/jlb.56.6.817

Sallusto, 1999, Two subsets of memory T lymphocytes with distinct homing potentials and effector functions, Nature, 401, 708, 10.1038/44385

Schnaider, 2000, The Hsp90-specific inhibitor geldanamycin selectively disrupts kinase-mediated signaling events of T-lymphocyte activation, Cell Stress Chaper., 5, 52, 10.1379/1466-1268(2000)005<0052:THSIGS>2.0.CO;2

Schrum, 2000, Enhanced surface TCR replenishment mediated by CD28 leads to greater TCR engagement during primary stimulation, Int. Immunol., 12, 833, 10.1093/intimm/12.6.833

Schuh, 1998, The interleukin 2 receptor alpha chain/CD25 promoter is a target for nuclear factor of activated T cells, J. Exp. Med., 188, 1369, 10.1084/jem.188.7.1369

Sikora, 1992, Loss of transcription factor AP-1 DNA binding activity during lymphocyte aging in vivo, FEBS Lett., 312, 179, 10.1016/0014-5793(92)80930-F

Sitte, 2000, Protein oxidation and degradation during cellular senescence of human BJ fibroblasts: part I-effects of proliferative senescence, FASEB J., 14, 2495, 10.1096/fj.00-0209com

Song, 1992, Expression of c-fos, c-jun and jun-b in peripheral blood lymphocytes from young and elderly adults, Mech. Ageing Dev., 65, 149, 10.1016/0047-6374(92)90031-8

Sosinowski, 2000, Src-like adaptor protein (SLAP) is a negative regulator of T cell receptor signaling, J. Exp. Med., 191, 463, 10.1084/jem.191.3.463

Spencer, 1997, Constitutive activation of NF-kappa B in an animal model of aging, Int. Immunol., 9, 1581, 10.1093/intimm/9.10.1581

Steffens, 2000, Evaluation of thymopoiesis using T cell receptor excision circles (TRECs): Differential correlation between adult and pediatric TRECs and naive phenotypes, Clin. Immunol., 97, 95, 10.1006/clim.2000.4938

Steger, 1996, Morphologically and functionally intact dendritic cells can be derived from the peripheral blood of aged individuals, Clin. Exp. Immunol., 105, 544, 10.1046/j.1365-2249.1996.d01-790.x

Straten, 1999, In situ T cells in melanoma, Cancer Immunol. Immunother., 48, 386, 10.1007/s002620050591

Tafuri, 2001, ICOS is essential for effective T-helper-cell responses, Nature, 409, 105, 10.1038/35051113

Tamir, 2000, Age-dependent alterations in the assembly of signal transduction complexes at the site of T cell/APC interaction, J. Immunol., 165, 1243, 10.4049/jimmunol.165.3.1243

Tamura, 2000, Molecular mechanism of the impairment in activation signal transduction in CD4(+) T cells from old mice, Int. Immunol., 12, 1205, 10.1093/intimm/12.8.1205

Tinkle, 1998, Decreased association of p56(lck) with CD4 may account for lowered tyrosine kinase activity in mitogen-activated human T lymphocytes during aging, Cell Immunol., 186, 154, 10.1006/cimm.1998.1313

Tortorella, 1997, Age-related impairment of T cell proliferative responses related to the decline of CD28(+) T cell subsets, Arch. Gerontol. Geriatr., 26, 55, 10.1016/S0167-4943(97)00033-2

Trebilcock, 1996, Evidence for lowered induction of nuclear factor kappa B in activated human T lymphocytes during aging, Gerontology, 42, 137, 10.1159/000213785

Trebilcock, 1996, Induction and regulation of NF kappa B during aging: Role of protein kinases, Clin. Immunol. Immunopathol., 79, 87, 10.1006/clin.1996.0054

Tugores, 1992, Human T-cell activation through the activation-inducer molecule/CD69 enhances the activity of transcription factor-AP-1, J. Immunol., 148, 2300, 10.4049/jimmunol.148.7.2300

Utsuyama, 1993, Influence of age on the signal transduction of T cells in mice, Int. Immunol., 9, 1177, 10.1093/intimm/5.9.1177

Utsuyama, 1997, Impairment of signal transduction in T cells from old mice, Mech. Ageing Dev., 93, 131, 10.1016/S0047-6374(96)01837-4

Vallejo, 1998, Aging-related deficiency of CD28 expression in CD4+ T cells is associated with the loss of gene-specific nuclear factor binding activity, J. Biol. Chem., 273, 8119, 10.1074/jbc.273.14.8119

Vallejo, 1999, Modulation of CD28 expression: Distinct regulatory pathways during activation and replicative senescence, J. Immunol., 162, 6572, 10.4049/jimmunol.162.11.6572

Van Gool, 1999, Blocking CD40-CD154 and CD80/CD86-CD28 interactions during primary allogeneic stimulation results in T cell anergy and high IL-10 production, Eur. J. Immunol., 29, 2367, 10.1002/(SICI)1521-4141(199908)29:08<2367::AID-IMMU2367>3.0.CO;2-3

Venable, 1999, Phospholipase D in cellular senescence Bba, Mol. Cell. Biol. Lipids, 1439, 291, 10.1016/S1388-1981(99)00101-8

Wakikawa, 1997, Altered expression of various receptors on T cells in young and old mice after mitogenic stimulation: A flow cytometric analysis, Mech. Ageing Dev., 94, 113, 10.1016/S0047-6374(97)01880-0

Walker, 1998, Down-regulation of CD28 via Fas (CD95): Influence of CD28 on T-cell apoptosis, Immunology, 94, 41, 10.1046/j.1365-2567.1998.00490.x

Weyand, 1998, Functional properties of CD4+CD28− T cells in the aging immune system, Mech. Ageing Dev., 102, 131, 10.1016/S0047-6374(97)00161-9

Whisler, 1991, Characterization of intracellular ionized calcium responsiveness and inisitol phosphate production among resting and stimulated peripheral blood T cells from elderly humans, Aging: Immunol. Infect. Dis., 3, 27

Whisler, 1993, Reduced activation of transcriptional factor-AP-1 among peripheral blood T-cells from elderly humans after PHA stimulation-restorative effect of phorbol diesters, Cell Immunol., 152, 96, 10.1006/cimm.1993.1270

Whisler, 1995, Differential expression of the alpha- and beta-isoforms of protein kinase C in peripheral blood T and B cells from young and elderly adults, Mech. Ageing Dev., 77, 197, 10.1016/0047-6374(94)01526-R

Whisler, 1996, Age-related decreases in IL-2 production by human T cells are associated with impaired activation of nuclear transcriptional factors AP-1 and NF-AT, Cell Immunol., 169, 185, 10.1006/cimm.1996.0109

Whisler, 1996, Age-related reductions in the activation of mitogen-activated protein kinases p44(mapk)/ERK1 and p42(mapk)/ERK2 in human T cells stimulated via ligation of the T cell receptor complex, Cell Immunol., 168, 201, 10.1006/cimm.1996.0067

Whisler, 1997, Expression and catalytic activities of protein tyrosine kinases (PTKs) Fyn and Lck in peripheral blood T cells from elderly humans stimulated through the T cell receptor (TCR)/CD3 complex, Mech. Ageing Dev., 98, 57, 10.1016/S0047-6374(97)00073-0

Whisler, 1998, Phosphorylation and coupling of zeta-chains to activated T-cell receptor (TCR)/CD3 complexes from peripheral blood T-cells of elderly humans, Mech. Ageing Dev., 105, 115, 10.1016/S0047-6374(98)00084-0

Whisler, 1999, Age-related impairments in TCR/CD3 activation of ZAP-70 are associated with reduced tyrosine phosphorylations of zeta-chains and p59(Fyn)/p56(Lck) in human T cells, Mech. Ageing Dev., 111, 49, 10.1016/S0047-6374(99)00074-3

Witkowski, 1999, Calcium signal abnormalities in murine T lymphocytes that express the multidrug transporter P-glycoprotein, Mech. Ageing Dev., 107, 165, 10.1016/S0047-6374(98)00147-X

Witkowski, 1996, Reciprocal expression of P-glycoprotein and TAP1 accompanied by higher expression of MHC class I antigens in T cells of old mice, J. Gerontol. Ser. A—Biol. Sci. Med., 51, B76, 10.1093/gerona/51A.1.B76

Yang, 1999, Cluster formation by protein kinase C theta during murine T cell activation: Effect of age, Cell Immunol., 195, 28, 10.1006/cimm.1999.1517

Young, 2001, Preliminary studies on the effect of dehydroepiandrosterone (DHEA) on both constitutive and phytohaemagglutinin (PHA)-inducible IL-6 and IL-2 mRNA expression and cytokine production in human spleen mononuclear cell suspensions in vitro, Clin. Exp. Immunol., 123, 28, 10.1046/j.1365-2249.2001.01445.x

Yu, 2001, The proteasome regulates receptor-mediated endocytosis of interleukin-2, J. Biol. Chem., 276, 381, 10.1074/jbc.M007991200