The role of the thymus in HIV infection: a 10 year perspective

AIDS - Tập 22 Số 2 - Trang 171-184 - 2008
Raphaël Ho Tsong Fang1, Arnaud D. Colantonio2, Christel H. Uíttenbogaart3
1Current address: Hôpital Necker-Enfants malades, Unité développement normal et pathologique du système immunitaire, INSERM U-768, 149, rue de Sèvres, 75015 Paris, France.; Departments of Microbiology, Immunology, and Molecular Genetics, USA
2Departments of Microbiology, Immunology, and Molecular Genetics, USA
3Jonsson Comprehensive Cancer Center, David E. Geffen School of Medicine at UCLA, Los Angeles, California, USA.; Pediatrics, USA; UCLA AIDS Institute, USA

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Kong, 1999, T cell receptor gene deletion circles identify recent thymic emigrants in the peripheral T cell pool, Proc Natl Acad Sci U S A, 96, 1536, 10.1073/pnas.96.4.1536

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

Rizk, 1972, Rebound enlargement of the thymus after successful corrective surgery for transposition of the great vessels, Am J Roentgenol Radium Ther Nucl Med, 116, 528, 10.2214/ajr.116.3.528

Hellerstein, 1999, Measurement of T-cell kinetics: recent methodologic advances, Immunol Today, 20, 438, 10.1016/S0167-5699(99)01529-7

Hellerstein, 2003, Subpopulations of long-lived and short-lived T cells in advanced HIV-1 infection, J Clin Invest, 112, 956, 10.1172/JCI200317533

Harris, 2005, Multiparameter evaluation of human thymic function: interpretations and caveats, Clin Immunol, 115, 138, 10.1016/j.clim.2004.12.008

Mackall, 1995, Age, Thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy, N Engl J Med, 332, 143, 10.1056/NEJM199501193320303

Hakim, 2005, Age-dependent incidence, time course, and consequences of thymic renewal in adults, J Clin Invest, 115, 930, 10.1172/JCI200522492

Kovacs, 2001, Identification of dynamically distinct subpopulations of T lymphocytes that are differentially affected by HIV, J Exp Med, 194, 1731, 10.1084/jem.194.12.1731

Lee, 2006, Thymic volume, T-cell populations, and parameters of thymopoiesis in adolescent and adult survivors of HIV infection acquired in infancy, AIDS, 20, 667, 10.1097/01.aids.0000216366.46195.81

Crivellato, 2004, Setting the stage: an anatomist's view of the immune system, Trends Immunol, 25, 210, 10.1016/j.it.2004.02.008

Bleul, 2006, Formation of a functional thymus initiated by a postnatal epithelial progenitor cell, Nature, 441, 992, 10.1038/nature04850

Rossi, 2006, Clonal analysis reveals a common progenitor for thymic cortical and medullary epithelium, Nature, 441, 988, 10.1038/nature04813

Haynes, 1988, Early events in human T cell ontogeny. Phenotypic characterization and immunohistologic localization of T cell precursors in early human fetal tissues, J Exp Med, 168, 1061, 10.1084/jem.168.3.1061

van Ewijk, 2000, Stepwise development of thymic microenvironments in vivo is regulated by thymocyte subsets, Development, 127, 1583, 10.1242/dev.127.8.1583

Boehm, 2006, Thymus-homing precursors and the thymic microenvironment, Trends Immunol, 27, 477, 10.1016/j.it.2006.08.004

Weerkamp, 2006, Human thymus contains multipotent progenitors with T/B lymphoid, myeloid, and erythroid lineage potential, Blood, 107, 3131, 10.1182/blood-2005-08-3412

Blom, 2006, Development of human lymphoid cells, Annu Rev Immunol, 24, 287, 10.1146/annurev.immunol.24.021605.090612

Weijer, 2002, Intrathymic and extrathymic development of human plasmacytoid dendritic cell precursors in vivo, Blood, 99, 2752, 10.1182/blood.V99.8.2752

Haddad, 2006, Dynamics of thymus-colonizing cells during human development, Immunity, 24, 217, 10.1016/j.immuni.2006.01.008

Blom, 1997, Prethymic CD34+ progenitors capable of developing into T cells are not committed to the T cell lineage, J Immunol, 158, 3571, 10.4049/jimmunol.158.8.3571

Haddad, 2004, Molecular characterization of early human T/NK and B-lymphoid progenitor cells in umbilical cord blood, Blood, 104, 3918, 10.1182/blood-2004-05-1845

Hao, 2001, Identification of a novel, human multilymphoid progenitor in cord blood, Blood, 97, 3683, 10.1182/blood.V97.12.3683

Hoebeke, 2007, T-, B- and NK-lymphoid, but not myeloid cells arise from human CD34(+)CD38(-)CD7(+) common lymphoid progenitors expressing lymphoid-specific genes, Leukemia, 21, 311, 10.1038/sj.leu.2404488

Ishii, 1999, Expression of stromal cell-derived factor-1/pre-B cell growth-stimulating factor receptor, CXC chemokine receptor 4, on CD34+ human bone marrow cells is a phenotypic alteration for committed lymphoid progenitors, J Immunol, 163, 3612, 10.4049/jimmunol.163.7.3612

Galy, 1993, Precursors of CD3+CD4+CD8+ cells in the human thymus are defined by expression of CD34. Delineation of early events in human thymic development, J Exp Med, 178, 391, 10.1084/jem.178.2.391

Spits, 2002, Development of alphabeta T cells in the human thymus, Nat Rev Immunol, 2, 760, 10.1038/nri913

Poulin, 1999, Direct evidence for thymic function in adult humans, J Exp Med, 190, 479, 10.1084/jem.190.4.479

Dion, 2004, HIV infection rapidly induces and maintains a substantial suppression of thymocyte proliferation, Immunity, 21, 757, 10.1016/j.immuni.2004.10.013

Plum, 1996, Interleukin-7 is a critical growth factor in early human T-cell development, Blood, 88, 4239, 10.1182/blood.V88.11.4239.bloodjournal88114239

Pallard, 1999, Distinct roles of the phosphatidylinositol 3-kinase and STAT5 pathways in IL-7-mediated development of human thymocyte precursors, Immunity, 10, 525, 10.1016/S1074-7613(00)80052-7

Garcia-Peydro, 2006, Notch1 and IL-7 receptor interplay maintains proliferation of human thymic progenitors while suppressing non-T cell fates, J Immunol, 177, 3711, 10.4049/jimmunol.177.6.3711

Okamoto, 2002, Effects of exogenous interleukin-7 on human thymus function, Blood, 99, 2851, 10.1182/blood.V99.8.2851

Napolitano, 2003, Effects of IL-7 on early human thymocyte progenitor cells in vitro and in SCID-hu Thy/Liv mice, J Immunol, 171, 645, 10.4049/jimmunol.171.2.645

Vollger, 1993, Interleukin-7 promotes the generation of phenotypically mature CD45RA positive human thymocytes in-vitro, Cytokine, 5, 157, 10.1016/1043-4666(93)90055-A

Hassan, 2001, Human recent thymic emigrants–identification, expansion, and survival characteristics, J Immunol, 167, 1970, 10.4049/jimmunol.167.4.1970

Schonland, 2003, Homeostatic control of T-cell generation in neonates, Blood, 102, 1428, 10.1182/blood-2002-11-3591

Swainson, 2007, IL-7-induced proliferation of recent thymic emigrants requires activation of the PI3K pathway, Blood, 109, 1034, 10.1182/blood-2006-06-027912

Fry, 2005, The many faces of IL-7: from lymphopoiesis to peripheral T cell maintenance, J Immunol, 174, 6571, 10.4049/jimmunol.174.11.6571

Seggewiss, 2007, Keratinocyte growth factor augments immune reconstitution after autologous hematopoietic progenitor cell transplantation in rhesus macaques, Blood, 110, 441, 10.1182/blood-2006-12-065623

Min, 2002, Protection from thymic epithelial cell injury by keratinocyte growth factor: a new approach to improve thymic and peripheral T-cell reconstitution after bone marrow transplantation, Blood, 99, 4592, 10.1182/blood.V99.12.4592

Kitchen, 1997, CXCR4 expression during lymphopoiesis: implications for human immunodeficiency virus type 1 infection of the thymus, J Virol, 71, 6928, 10.1128/JVI.71.9.6928-6934.1997

Berkowitz, 1998, CXCR4 and CCR5 expression delineates targets for HIV-1 disruption of T cell differentiation, J Immunol, 161, 3702, 10.4049/jimmunol.161.7.3702

Zaitseva, 1998, CXCR4 and CCR5 on human thymocytes: biological function and role in HIV-1 infection, J Immunol, 161, 3103, 10.4049/jimmunol.161.6.3103

Zhang, 1998, In vivo distribution of the human immunodeficiency virus/simian immunodeficiency virus coreceptors: CXCR4, CCR3, and CCR5, J Virol, 72, 5035, 10.1128/JVI.72.6.5035-5045.1998

Pedroza-Martins, 1998, Differential tropism and replication kinetics of human immunodeficiency virus type 1 isolates in thymocytes: coreceptor expression allows viral entry, but productive infection of distinct subsets is determined at the postentry level, J Virol, 72, 9441, 10.1128/JVI.72.12.9441-9452.1998

Gurney, 2006, Human immunodeficiency virus persistence and production in T-cell development, Clin Vaccine Immunol, 13, 1237, 10.1128/CVI.00184-06

Hernandez-Lopez, 2002, Stromal cell-derived factor 1/CXCR4 signaling is critical for early human T-cell development, Blood, 99, 546, 10.1182/blood.V99.2.546

Savino, 2002, The thymus gland: a target organ for growth hormone, Scand J Immunol, 55, 442, 10.1046/j.1365-3083.2002.01077.x

Maggiano, 1994, Detection of growth hormone-producing cells in human thymus by immunohistochemistry and nonradioactive in situ hybridization, J Histochem Cytochem, 42, 1349, 10.1177/42.10.7930517

Hanley, 2005, Growth hormone-induced stimulation of multilineage human hematopoiesis, Stem Cells, 23, 1170, 10.1634/stemcells.2004-0322

Napolitano, 2002, Increased thymic mass and circulating naive CD4 T cells in HIV-1-infected adults treated with growth hormone, AIDS, 16, 1103, 10.1097/00002030-200205240-00003

Jamieson, 1999, Generation of functional thymocytes in the human adult, Immunity, 10, 569, 10.1016/S1074-7613(00)80056-4

Haynes, 2000, The human thymus during aging, Immunol Res, 22, 253, 10.1385/IR:22:2-3:253

Zhang, 1999, Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy, J Exp Med, 190, 725, 10.1084/jem.190.5.725

Sempowski, 2000, Leukemia inhibitory factor, oncostatin M, IL-6, and stem cell factor mRNA expression in human thymus increases with age and is associated with thymic atrophy, J Immunol, 164, 2180, 10.4049/jimmunol.164.4.2180

Min, 2007, Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging, Blood, 109, 2529, 10.1182/blood-2006-08-043794

Deng, 1996, Identification of a major co-receptor for primary isolates of HIV-1, Nature, 381, 661, 10.1038/381661a0

Dragic, 1996, HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5, Nature, 381, 667, 10.1038/381667a0

Feng, 1996, HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane G protein-coupled receptor, Science, 272, 872, 10.1126/science.272.5263.872

Kitchen, 1999, Distribution of the human immunodeficiency virus coreceptors CXCR4 and CCR5 in fetal lymphoid organs: implications for pathogenesis in utero, AIDS Res Hum Retroviruses, 15, 143, 10.1089/088922299311565

Zamarchi, 2002, Expression and functional activity of CXCR-4 and CCR-5 chemokine receptors in human thymocytes, Clin Exp Immunol, 127, 321, 10.1046/j.1365-2249.2002.01775.x

Keir, 2002, IFN-alpha secretion by type 2 predendritic cells up-regulates MHC class I in the HIV-1-infected thymus, J Immunol, 168, 325, 10.4049/jimmunol.168.1.325

Gurney, 2004, Endogenous IFN-alpha production by plasmacytoid dendritic cells exerts an antiviral effect on thymic HIV-1 infection, J Immunol, 173, 7269, 10.4049/jimmunol.173.12.7269

Schmitt, 2006, Differential susceptibility of human thymic dendritic cell subsets to X4 and R5 HIV-1 infection, AIDS, 20, 533, 10.1097/01.aids.0000210607.63138.bc

Gurney, 2002, TCR gamma delta+ and CD161+ thymocytes express HIV-1 in the SCID-hu mouse, potentially contributing to immune dysfunction in HIV infection, J Immunol, 169, 5338, 10.4049/jimmunol.169.9.5338

Joshi, 1986, Thymus biopsy in children with acquired immunodeficiency syndrome, Arch Pathol Lab Med, 110, 837

Baskin, 1991, Thymus in simian immunodeficiency virus-infected rhesus monkeys, Lab Invest, 65, 400

Papiernik, 1992, Thymic abnormalities in fetuses aborted from human immunodeficiency virus type 1 seropositive women, Pediatrics, 89, 297, 10.1542/peds.89.2.297

Jamieson, 1995, In vivo pathogenic properties of two clonal human immunodeficiency virus type 1 isolates, J Virol, 69, 6259, 10.1128/JVI.69.10.6259-6264.1995

Uittenbogaart, 1996, Differential tropism of HIV-1 isolates for distinct thymocyte subsets in vitro, Aids, 10, F9, 10.1097/00002030-199606001-00001

Lee, 1997, Human immunodeficiency virus type 1 infection of mature CD3hiCD8+ thymocytes, J Virol, 71, 6671, 10.1128/JVI.71.9.6671-6676.1997

Haynes, 1999, Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection, J Clin Invest, 103, 453, 10.1172/JCI5201

Grody, 1985, Thymus involution in the acquired immunodeficiency syndrome, Am J Clin Pathol, 84, 85, 10.1093/ajcp/84.1.85

Sopper, 2003, Impact of simian immunodeficiency virus (SIV) infection on lymphocyte numbers and T-cell turnover in different organs of rhesus monkeys, Blood, 101, 1213, 10.1182/blood-2002-06-1644

Arron, 2005, Impact of thymectomy on the peripheral T cell pool in rhesus macaques before and after infection with simian immunodeficiency virus, Eur J Immunol, 35, 46, 10.1002/eji.200424996

Halnon, 2005, Thymic function and impaired maintenance of peripheral T cell populations in children with congenital heart disease and surgical thymectomy, Pediatr Res, 57, 42, 10.1203/01.PDR.0000147735.19342.DE

Heitger, 2000, Requirement of residual thymus to restore normal T-cell subsets after human allogeneic bone marrow transplantation, Transplantation, 69, 2366, 10.1097/00007890-200006150-00026

Heitger, 1997, Essential role of the thymus to reconstitute naive (CD45RA+) T-helper cells after human allogeneic bone marrow transplantation, Blood, 90, 850, 10.1182/blood.V90.2.850

Terszowski, 2006, Evidence for a functional second thymus in mice, Science, 312, 284, 10.1126/science.1123497

von Boehmer, 2006, Immunology. Thoracic thymus, exclusive no longer, Science, 312, 206, 10.1126/science.1126403

Ho Tsong Fang, 2006, HIV and the hidden face of the thymus, AIDS, 20, 2240, 10.1097/01.aids.0000252058.69254.a2

Khariwala, 2004, Cervical presentations of thymic anomalies in children, Int J Pediatr Otorhinolaryngol, 68, 909, 10.1016/j.ijporl.2004.02.012

Arellano, 2006, Thymic function-related markers within the thymus and peripheral blood: Are they comparable?, J Clin Immunol, 26, 96, 10.1007/s10875-006-7519-7

Sodora, 2000, Quantification of thymic function by measuring T cell receptor excision circles within peripheral blood and lymphoid tissues in monkeys, Eur J Immunol, 30, 1145, 10.1002/(SICI)1521-4141(200004)30:4<1145::AID-IMMU1145>3.0.CO;2-7

Hatzakis, 2000, Effect of recent thymic emigrants on progression of HIV-1 disease, Lancet, 355, 599, 10.1016/S0140-6736(99)10311-8

Richardson, 2004, T-cell receptor excision circles (TREC) in SHIV 89.6p and SIVmac251 models of HIV-1 infection, DNA Cell Biol, 23, 1, 10.1089/104454904322745880

Goedert, 2001, T cell receptor excision circles and HIV-1 2-LTR episomal DNA to predict AIDS in patients not receiving effective therapy, Aids, 15, 2245, 10.1097/00002030-200111230-00005

van Asten, 2004, Preseroconversion immune status predicts the rate of CD4 T cell decline following HIV infection, AIDS, 18, 1885, 10.1097/00002030-200409240-00004

Hazenberg, 2000, Increased cell division but not thymic dysfunction rapidly affects the T-cell receptor excision circle content of the naive T cell population in HIV-1 infection, Nat Med, 6, 1036, 10.1038/79549

Sachsenberg, 1998, Turnover of CD4+ and CD8+ T lymphocytes in HIV-1 infection as measured by Ki-67 antigen, J Exp Med, 187, 1295, 10.1084/jem.187.8.1295

Monceaux, 2003, Distinct cycling CD4(+)- and CD8(+)-T-cell profiles during the asymptomatic phase of simian immunodeficiency virus SIVmac251 infection in rhesus macaques, J Virol, 77, 10047, 10.1128/JVI.77.18.10047-10059.2003

Combadere, 2000, CD4+Ki67+ lymphocytes in HIV-infected patients are effector T cells accumulated in the G1 phase of the cell cycle, Eur J Immunol, 30, 3598, 10.1002/1521-4141(200012)30:12<3598::AID-IMMU3598>3.0.CO;2-E

Hazenberg, 2003, Thymic output: a bad TREC record, Nat Immunol, 4, 97, 10.1038/ni0203-97

Sodora, 2002, Decreased levels of recent thymic emigrants in peripheral blood of simian immunodeficiency virus-infected macaques correlate with alterations within the thymus, J Virol, 76, 9981, 10.1128/JVI.76.19.9981-9990.2002

Wykrzykowska, 1998, Early regeneration of thymic progenitors in rhesus macaques infected with simian immunodeficiency virus, J Exp Med, 187, 1767, 10.1084/jem.187.11.1767

Ho Tsong Fang, 2005, Disease progression in macaques with low SIV replication levels: on the relevance of TREC counts, AIDS, 19, 663, 10.1097/01.aids.0000166089.93574.5a

Viollet, 2006, Death of CD4+ T cells from lymph nodes during primary SIVmac251 infection predicts the rate of AIDS progression, J Immunol, 177, 6685, 10.4049/jimmunol.177.10.6685

Hellerstein, 1999, Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans, Nat Med, 5, 83, 10.1038/4772

Sempowski, 2005, Naive T cells are maintained in the periphery during the first 3 months of acute HIV-1 infection: implications for analysis of thymus function, J Clin Immunol, 25, 462, 10.1007/s10875-005-5635-4

Nobile, 2004, De novo T-cell generation in patients at different ages and stages of HIV-1 disease, Blood, 104, 470, 10.1182/blood-2003-12-4265

McCune, 1998, High prevalence of thymic tissue in adults with human immunodeficiency virus-1 infection, J Clin Invest, 101, 2301, 10.1172/JCI2834

Autran, 1997, Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease, Science, 277, 112, 10.1126/science.277.5322.112

Pakker, 1998, Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation, Nat Med, 4, 208, 10.1038/nm0298-208

Zhang, 1998, Kinetics of CD4+ T cell repopulation of lymphoid tissues after treatment of HIV-1 infection, Proc Natl Acad Sci U S A, 95, 1154, 10.1073/pnas.95.3.1154

Smith, 2000, Thymic size and lymphocyte restoration in patients with human immunodeficiency virus infection after 48 weeks of zidovudine, lamivudine, and ritonavir therapy, J Infect Dis, 181, 141, 10.1086/315169

Krogstad, 1999, Primary HIV infection of infants: the effects of somatic growth on lymphocyte and virus dynamics, Clin Immunol, 92, 25, 10.1006/clim.1999.4728

Resino, 2006, Different profiles of immune reconstitution in children and adults with HIV-infection after highly active antiretroviral therapy, BMC Infect Dis, 6, 112, 10.1186/1471-2334-6-112

Vigano, 1999, Thymus volume correlates with the progression of vertical HIV infection, AIDS, 13, F29, 10.1097/00002030-199904010-00001

Gorochov, 1998, Perturbation of CD4+ and CD8+ T-cell repertoires during progression to AIDS and regulation of the CD4+ repertoire during antiviral therapy, Nat Med, 4, 215, 10.1038/nm0298-215

Connors, 1997, HIV infection induces changes in CD4+ T-cell phenotype and depletions within the CD4+ T-cell repertoire that are not immediately restored by antiviral or immune-based therapies, Nat Med, 3, 533, 10.1038/nm0597-533

Cossarizza, 2004, Highly active antiretroviral therapy restores CD4+ Vbeta T-cell repertoire in patients with primary acute HIV infection but not in treatment-naive HIV+ patients with severe chronic infection, J Acquir Immune Defic Syndr, 35, 213, 10.1097/00126334-200403010-00001

Hardy, 2004, Evidence of thymic reconstitution after highly active antiretroviral therapy in HIV-1 infection, HIV Med, 5, 67, 10.1111/j.1468-1293.2004.00187.x

Fernandez, 2006, Thymic function in severely immunodeficient HIV type 1-infected patients receiving stable and effective antiretroviral therapy, AIDS Res Hum Retroviruses, 22, 163, 10.1089/aid.2006.22.163

Mackall, 1996, Thymic-independent T cell regeneration occurs via antigen-driven expansion of peripheral T cells resulting in a repertoire that is limited in diversity and prone to skewing, J Immunol, 156, 4609, 10.4049/jimmunol.156.12.4609

Sarzotti, 2003, T cell repertoire development in humans with SCID after nonablative allogeneic marrow transplantation, J Immunol, 170, 2711, 10.4049/jimmunol.170.5.2711

Markert, 2001, Thymopoiesis in HIV-infected adults after highly active antiretroviral therapy, AIDS Res Hum Retroviruses, 17, 1635, 10.1089/088922201753342040

Ruiz-Mateos, 2004, Thymic volume is associated independently with the magnitude of short- and long-term repopulation of CD4+ T cells in HIV-infected adults after highly active antiretroviral therapy (HAART), Clin Exp Immunol, 136, 501, 10.1111/j.1365-2249.2004.02474.x

Franco, 2002, T-cell repopulation and thymic volume in HIV-1-infected adult patients after highly active antiretroviral therapy, Blood, 99, 3702, 10.1182/blood.V99.10.3702

Delgado, 2002, Evidence of thymic function in heavily antiretroviral-treated human immunodeficiency virus type 1-infected adults with long-term virologic treatment failure, J Infect Dis, 186, 410, 10.1086/341561

Delobel, 2006, Naive T-cell depletion related to infection by X4 human immunodeficiency virus type 1 in poor immunological responders to highly active antiretroviral therapy, J Virol, 80, 10229, 10.1128/JVI.00965-06

McCune, 2000, Factors influencing T-cell turnover in HIV-1-seropositive patients, J Clin Invest, 105, R1, 10.1172/JCI8647

Pido-Lopez, 2003, Thymic output during initial highly active antiretroviral therapy (HAART) and during HAART supplementation with interleukin 2 and/or with HIV type 1 immunogen (Remune), AIDS Res Hum Retroviruses, 19, 103, 10.1089/088922203762688603

Walker, 1998, Peripheral expansion of preexisting mature T cells is an important means of CD4+ T-cell regeneration HIV-infected adults, Nat Med, 4, 852, 10.1038/nm0798-852

Gutierrez, 2006, Disseminate and fatal cytomegalovirus disease with thymitis in a naive HIV-patient after early initiation of HAART: immune restoration disease?, J Clin Virol, 36, 13, 10.1016/j.jcv.2005.12.007

French, 2004, Graves' disease during immune reconstitution after highly active antiretroviral therapy for HIV infection: evidence of thymic dysfunction, AIDS Res Hum Retroviruses, 20, 157, 10.1089/088922204773004879

Kaufmann, 1998, CD4-cell count in HIV-1-infected individuals remaining viraemic with highly active antiretroviral therapy (HAART). Swiss HIV Cohort Study, Lancet, 351, 723, 10.1016/S0140-6736(98)24010-4

Stoddart, 2001, Impaired replication of protease inhibitor-resistant HIV-1 in human thymus, Nat Med, 7, 712, 10.1038/89090

Lecossier, 2001, Discordant increases in CD4+ T cells in human immunodeficiency virus-infected patients experiencing virologic treatment failure: role of changes in thymic output and T cell death, J Infect Dis, 183, 1009, 10.1086/319285

Cohen Stuart, 1998, Early recovery of CD4+ T lymphocytes in children on highly active antiretroviral therapy. Dutch study group for children with HIV infections, AIDS, 12, 2155, 10.1097/00002030-199816000-00010

Essajee, 1999, Immunologic and virologic responses to HAART in severely immunocompromised HIV-1-infected children, AIDS, 13, 2523, 10.1097/00002030-199912240-00005

Saitoh, 2006, Association of CD4+ T-lymphocyte counts and new thymic emigrants in HIV-infected children during successful highly active antiretroviral therapy, J Allergy Clin Immunol, 117, 909, 10.1016/j.jaci.2006.01.013

De Rossi, 2005, Relationship between changes in thymic emigrants and cell-associated HIV-1 DNA in HIV-1-infected children initiating antiretroviral therapy, Antivir Ther, 10, 63, 10.1177/135965350501000104

Solomon, 2003, Immunological and virological failure after antiretroviral therapy is associated with enhanced peripheral and thymic pathogenicity, J Infect Dis, 187, 1915, 10.1086/375351

Dion, 2007, Slow disease progression and robust therapy-mediated CD4+ T-cell recovery are associated with efficient thymopoiesis during HIV-1 infection, Blood, 109, 2912, 10.1182/blood-2006-09-047308

Teixeira, 2001, Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect lower thymic function, AIDS, 15, 1749, 10.1097/00002030-200109280-00002

Duus, 2001, Separation of human immunodeficiency virus type 1 replication from nef-mediated pathogenesis in the human thymus, J Virol, 75, 3916, 10.1128/JVI.75.8.3916-3924.2001

Storek, 2003, Interleukin-7 improves CD4 T-cell reconstitution after autologous CD34 cell transplantation in monkeys, Blood, 101, 4209, 10.1182/blood-2002-08-2671

Fry, 2003, IL-7 therapy dramatically alters peripheral T-cell homeostasis in normal and SIV-infected nonhuman primates, Blood, 101, 2294, 10.1182/blood-2002-07-2297

Beq, 2006, IL-7 induces immunological improvement in SIV-infected rhesus macaques under antiviral therapy, J Immunol, 176, 914, 10.4049/jimmunol.176.2.914

Albuquerque, 2007, Rate of increase in circulating IL-7 and loss of IL-7Ralpha expression differ in HIV-1 and HIV-2 infections: two lymphopenic diseases with similar hyperimmune activation but distinct outcomes, J Immunol, 178, 3252, 10.4049/jimmunol.178.5.3252

Sutherland, 2005, Activation of thymic regeneration in mice and humans following androgen blockade, J Immunol, 175, 2741, 10.4049/jimmunol.175.4.2741

Pedroza-Martins, 2002, Impact of cytokines on replication in the thymus of primary human immunodeficiency virus type 1 isolates from infants, J Virol, 76, 6929, 10.1128/JVI.76.14.6929-6943.2002