dx.doi.org

Memory T Cells in Rhesus Macaques

  • Picker LJ, Siegelman MH. Lymphoid organs and tissues. In: Paul WE, ed. Fundamental Immunology, 4th ed. Philadelphia: Lippincott-Raven, 1999:14, 479.

    Google Scholar 

  • Picker LJ, Terstappen LW, Rott LS et al. Differential expression of homing-associated adhesion molecules by T-cell subsets in man. J Immunol 1990; 145:3247–3255.

    CAS  PubMed  Google Scholar 

  • Mestas J, Hughes CCW. Of mice and not men: differences between mouse and human immunology. J Immunol 2004; 172:2731–2738.

    CAS  PubMed  Google Scholar 

  • ACLAM [American College of Laboratory Animal Medicine]. Public statement: medical records for animals used in research, teaching and testing. ILAR journal 2007; 48(1). Public statement.

    Google Scholar 

  • Conlee KM, Hoffeld EH, Stephens ML. A demographic analysis of primate research in the United States. ATLA (Alternatives to Laboratory Animals) 2004; 32(1):315–322.

    CAS  Google Scholar 

  • Desrosiers RC. The simian immunodeficiency viruses. Annu Rev Immunol 1990; 8:557–578.

    Article  CAS  PubMed  Google Scholar 

  • Pilcher CD, Wohl DA, Hicks CB. Diagnosing primary HIV infection. Ann Int Med 2002; 136(6):488–489.

    PubMed  Google Scholar 

  • Pal R, Venzon D, Letvin NL et al. ALVAC-SIV-gag-pol-env-based vaccination and macaque major histocompatibility complex class I (A*01) delay simian immunodeficiency virus SIV(mac)-induced immunodeficiency. J Virol 2001; 76(1):292–302.

    Article  Google Scholar 

  • Parker RA, Regan MM, Reimann KA. Variability of viral load in plasma of Rhesus monkeys inoculated with simian immunodeficiency virus or simian/human immunodeficiency virus: implications for using non-human primate AIDS models to test vaccines and therapeutics. J Virol 2001; 75(22):11234–11238.

    Article  CAS  PubMed  Google Scholar 

  • Pitcher CJ, Hagen SI, Walker JM et al. Development and homeostasis of T-cell memory in Rhesus macaque. J Immunol 2002; 168:29–43.

    CAS  PubMed  Google Scholar 

  • De Rosa SC, Herzenberg LA, Roederer M. 11-color, 13-parameter flow cytometry: identification of human naive T-cells by phenotype, function and T-cell receptor diversity. Nat Med 2001; 7:245–248.

    Article  PubMed  CAS  Google Scholar 

  • Walker JM, Maecker HT, Maino VC et al. Multicolor flow cytometric analysis in SIV-infected Rhesus macaque. Methods Cell Biol 2004; 75:535–557.

    Article  PubMed  Google Scholar 

  • Sallusto F, Lenig D, Förster R et al. Two subsets of memory T-lymphocytes with distinct homing potentials and effector functions. Nature 1999; 401(6754):708–712.

    Article  CAS  PubMed  Google Scholar 

  • Sallusto F, Geginat J, Lanzavecchia A. Central memory and effector memory T-cell subsets: function, generation and maintenance. Annual Review of Immunology 2004; 22:745–763.

    Article  CAS  PubMed  Google Scholar 

  • Lanzavecchia A, Sallusto F. Understanding the generation and function of memory T-cell subsets. Curr Opin Immunol 2005; 17(3):326–332.

    Article  CAS  PubMed  Google Scholar 

  • Masopust D, Vezys V, Marzo AL et al. Preferential localization of effector memory cells in nonlymphoid tissue. Science 2001; 291:2413–2417.

    Article  CAS  PubMed  Google Scholar 

  • Baron JL, Madri JA, Ruddle NH et al. Surface expression of α4 integrin by CD4 T-cells is required for their entry into brain parenchyma. J Exp Med 1993; 177:57–68.

    Article  CAS  PubMed  Google Scholar 

  • Wherry EJ, Teichgräber V, Becker TC et al. Lineage relationship and protective immunity of memory CD8 T-cell subsets. Nat Immunol 2003; 4(3):225–234.

    Article  CAS  PubMed  Google Scholar 

  • Vaccari M, Trindade CJ, Venzon D et al. Vaccine-induced CD8+ central memory T-cells in protection from simian AIDS. J Immunol 2005; 175:3502–3507.

    CAS  PubMed  Google Scholar 

  • Kenneth SC, Kaur A. Flow cytometric detection of degranulation reveals phenotypic heterogeneity of degranulating CMV-specific CD8+ T-lymphocytes in rhesus macaques. J Immunol Methods 2007; 325(1–2):20–34.

    Google Scholar 

  • Macchia I, Gauduin MC, Kaur A et al. Expression of CD8 alpha identifies a distinct subset of effector memory CD4+ T-lymphocytes. Immunology 2006; 119(2):232–242.

    Article  CAS  PubMed  Google Scholar 

  • Pahar B, Lackner AA, Veazey RS. Intestinal double-positive CD4+CD8+ T-cells are highly activated memory cells with an increased capacity to produce cytokines. Eu J Immunol 2006; 36(3):583–592.

    Article  CAS  Google Scholar 

  • Reiner ST, Sallusto F, Lanzavecchia A. Division of labor with a workforce of one: challenges in specifying effector and memory T-cell fate. Science 2007; 317(5838):622–625.

    Article  CAS  PubMed  Google Scholar 

  • Murphy KM, Reiner SL. The lineage decisions of helper T-cells. Nat Rev Immunol 2002; 2(12):933–44.

    Article  CAS  PubMed  Google Scholar 

  • Sakaguchi S, Powrie F. Emerging challenges in regulatory T-cell function and biology. Science 2007; 317(5838):627–629.

    Article  CAS  PubMed  Google Scholar 

  • Abbas AK, Murphy KM, Sher A. Functional diversity of helper T-lymphocytes. Nature 1996; 383:787–793.

    Article  CAS  PubMed  Google Scholar 

  • Romagnani S. Lymphokine production by human T-cells in disease states. Annu Rev Immunol 1994; 12:227–257.

    Article  CAS  PubMed  Google Scholar 

  • Levings MK, Sangregorio R, Roncarolo MG. Human CD25+CD4+ T regulatory cells suppress naive and memory T-cell proliferation and can be expanded in vitro without loss of function. J Exp Med 2001; 193:1295–1302.

    Article  CAS  PubMed  Google Scholar 

  • Sakaguchi S. Regulatory T-cells: key controllers of immunologic self-tolerance. Cell 2000; 101(5):455–458.

    Article  CAS  PubMed  Google Scholar 

  • Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T-cells in immunological tolerance to self and non-self. Nat Immunol 2005; 6(4):345–352.

    Article  CAS  PubMed  Google Scholar 

  • Sakaguchi S. Naturally arising CD4+ regulatory T-cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 2004; 22:531–562.

    Article  CAS  PubMed  Google Scholar 

  • Bluestone JA, Abbas AK. Natural versus adaptive regulatory T-cells. Nature Rev Immunol 2003; 3:253–257.

    Article  CAS  Google Scholar 

  • Sakaguchi S, Sakaguchi N, Asano M et al. Immunologic self-tolerance maintained by activated T-cells expressing IL-2 receptor a-chains. J Immunol 1995; 155: 1151–1164.

    CAS  PubMed  Google Scholar 

  • Malek TR, Yu A, Vincek V et al. CD4 regulatory T-cells prevent lethal autoimmunity in IL-2Rb-deficient mice. Implications for the nonredundant function of IL-2. Immunity 2002; 17:167–178.

    Article  CAS  PubMed  Google Scholar 

  • Salomon B, Lenschow D, Rhee L et al. B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T-cells that control autoimmune diabetes. Immunity 2000; 12:431–440.

    Article  CAS  PubMed  Google Scholar 

  • Shimizu J, Yamazaki S, Takahashi T et al. Stimulation of CD25+CD4+ regulatory T-cells through GITR breaks immunological self-tolerance. Nature Immunol 2002; 3:135–142.

    Article  CAS  Google Scholar 

  • Hori S, Nomura T, Sakaguchi S. Control of regulatory T-cell development by the transcription factor Foxp3. Science 2003; 299(5609):1057–1061.

    Article  CAS  PubMed  Google Scholar 

  • Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T-cells. Nat Immunol 2003; 4:330–336.

    Article  CAS  PubMed  Google Scholar 

  • Sugimoto N, Oida T, Hirota K et al. Foxp3-dependent and-independent molecules specific for CD25+CD4+ natural regulatory T-cells revealed by DNA microarray analysis. Int Immunol 2006; 18(8):1197–1209.

    Article  CAS  PubMed  Google Scholar 

  • Wildin RS, Freitas A. IPEX and FOXP3: clinical and research perspectives. J Autoimmun 2005; 25: (Suppl)56–62.

    Article  CAS  PubMed  Google Scholar 

  • Wildin RS, Smyk-Pearson S, Filipovich AH. Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J Med Genet 2002; 39(8):537–545.

    Article  CAS  PubMed  Google Scholar 

  • Liu W, Putnam AL, Xu-Yu Z et al. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med 2006; 203:1701–1711.

    Article  CAS  PubMed  Google Scholar 

  • Jonuleit H, Schmitt E, Stassen M et al. Identification and functional characterization of human CD4(+)CD25(+) T-cells with regulatory properties isolated from peripheral blood. J Exp Med 2001; 193:1285–1294.

    Article  CAS  PubMed  Google Scholar 

  • Nakamura K, Kitani A, Strober W. Cell contact-dependent immunosuppression by CD4(+)CD25(+) regulatory T-cells is mediated by cell surface-bound transforming growth factor beta. J Exp Med 2001; 194:629–644.

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez A, Andre-Schmutz I, Carnaud C et al. Damage control, rather than unresponsiveness, effected by protective DX5+ T-cells in autoimmune diabetes. Nature Immunol 2001; 2:1117–1125.

    Article  CAS  Google Scholar 

  • Barrat FJ, Cua DJ, Boonstra A et al. In vitro generation of interleukin-10-producing regulatory CD4+ T-cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (TH1)-and TH2-inducing cytokines. J Exp Med 2002; 195:603–616.

    Article  CAS  PubMed  Google Scholar 

  • Chatenoud L, Primo J, Bach JF. CD3 antibody-induced dominant self-tolerance in overtly diabetic NOD mice. J Immunol 1997; 158:2947–2954.

    CAS  PubMed  Google Scholar 

  • Maloy KJ, Powrie F. Regulatory T-cells in the control of immune pathology. Nature Immunol 2001; 2:816–822.

    Article  CAS  Google Scholar 

  • Kumanogoh A, Wang X, Lee I et al. Increased T-cell autoreactivity in the absence of CD40-CD40 ligand interactions: a role of CD40 in regulatory T-cell development. J Immunol 2001; 166:353–360.

    CAS  PubMed  Google Scholar 

  • Pacholczyk R, Kraj P, Ignatowicz L. Peptide specificity of thymic selection of CD4+CD25+ T-cells. J Immunol 2002; 168:613–620.

    CAS  PubMed  Google Scholar 

  • Bohling SD, Allison KH. Immunosuppressive regulatory T-cells are associated with aggressive breast cancer phenotypes: a potential therapeutic target. Mod Pathol 2008; 21(12):1527–1532.

    Article  CAS  PubMed  Google Scholar 

  • Ahmadzadeh M, Felipe-Silva A, Heemskerk B et al. FOXP3 expression accurately defines the population of intratumoral regulatory T-cells that selectively accumulate in metastatic melanoma lesions. Blood 2008; 112(13):4953–4960.

    Article  CAS  PubMed  Google Scholar 

  • Brivio F, Fumagalli L, Parolini D et al. T-helper/T-regulator lymphocyte ratio as a new immunobiological index to quantify the anticancer immune status in cancer patients. In Vivo 2008; 22(5):647–650.

    CAS  PubMed  Google Scholar 

  • Estes JD, Li Q, Reynolds MR et al. Premature induction of an immunosuppressive regulatory T-cell response during acute simian immunodeficiency virus infection. J Infect Dis 2006; 193:703–712.

    Article  CAS  PubMed  Google Scholar 

  • Hryniewicz A, Boasso A, Edghill-Smith Y et al. CTLA-4 blockade decreases TGF-ß, indoleamine 2,3-dioxygenase and viral RNA expression in tissues of SIVmac251-infected macaques. Blood 2006; 108:3834–3842.

    Article  CAS  PubMed  Google Scholar 

  • Boasso A, Vaccari M, Hryniewicz A et al. Regulatory T-cell markers, indoleamine (2,3)-dioxygenase and virus levels in spleen and gut during progressive SIV infection. J Virol 2007; 81:11593–11603.

    Article  CAS  PubMed  Google Scholar 

  • Kinter AL, Hennessey M, Bell A et al. CD25+CD4+ regulatory T-cells from the peripheral blood of asymptomatic HIV-infected individuals regulate CD4+ and CD8+ HIV-specific T-cell immune responses in vitro and are associated with favorable clinical markers of disease status. J Exp Med 2004; 200:331–343.

    Article  CAS  PubMed  Google Scholar 

  • Nilsson J, Boasso A, Velilla PA et al. HIV-1 driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS. Blood 2006; 108:3808–3817.

    Article  CAS  PubMed  Google Scholar 

  • Aandahl EM, Michaëlsson J, Moretto WJ et al. Human CD4+ CD25+ regulatory T-cells control T-cell responses to human immunodeficiency virus and cytomegalovirus antigens J Virol 2004; 78(5):2454–2459.

    Article  CAS  PubMed  Google Scholar 

  • Acosta-Rodriguez EV, Rivino L, Geqinat J et al. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol 2007; 8:639–646.

    Article  CAS  PubMed  Google Scholar 

  • Sher A, Coffman RL. Regulation of immunity to parasites by T-cells and T-cell-derived cytokines. Annu Rev Immunol 1992; 10:385–409.

    Article  CAS  PubMed  Google Scholar 

  • Ye P, Rodriguez FH, Kanaly S et al. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment and host defense. J Exp Med 2001; 194:519–527.

    Article  CAS  PubMed  Google Scholar 

  • Liang SC, Tan XY, Luxenberg DP et al. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 2006; 203:2271–2279.

    Article  CAS  PubMed  Google Scholar 

  • Cecchinato V, Trindade CJ, Laurence A et al. Altered balance between Th17 and Th1 cells at mucosal sites predicts AIDS progression in simian immunodeficiency virus-infected macaques. Mucosal Immunol 2008; 1(4):279–288.

    Article  CAS  PubMed  Google Scholar 

  • Brenchley JM, Paiardini M, Knoxs KS et al. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood 2008; 112(7):2826–2835.

    Article  CAS  PubMed  Google Scholar 

  • Raffatellu M, Santos RL, Verhoeven DE et al. Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat Med 2008; 14(4):421–428.

    Article  CAS  PubMed  Google Scholar 

  • Reinhardt RL, Khoruts A, Merica R et al. Visualizing the generation of memory CD4 T-cells in the whole body. Nature 2001; 410:101–105.

    Article  CAS  PubMed  Google Scholar 

  • Kodera M, Grailer JJ, Karalewitz AP et al. T Lymphocyte migration to lymph nodes is maintained during homeostatic proliferation. Microscopy and Microanalysis. Cambridge University Press 2008; 14:211–224.

    CAS  Google Scholar 

  • Weninger W, Crowley MA, Manjunath N et al. Migratory properties of naive, effector and memory CD8+ T-cells. J Exp Med 2001; 194(7):953–966.

    Article  CAS  PubMed  Google Scholar 

  • Mora JR, von Andrian UH. T-cell homing specificity and plasticity: new concepts and future challenges. Trends Immunol 2006; 27(5):235–243.

    Article  CAS  PubMed  Google Scholar 

  • Butcher EC, Picker LJ. Lymphocyte homing and homeostasis. Science 1996; 272(5258):60–66.

    Article  CAS  PubMed  Google Scholar 

  • Masopust D, Vezys V, Wherry EJ et al. Cutting edge: gut microenvironment promotes differentiation of a unique memory CD8 T-cell population. J Immunol 2006; 176:2079–2083.

    CAS  PubMed  Google Scholar 

  • Gowans JL, Knight EJ. The route of recirculation of lymphocytes in the rat. Proc R Soc Lond B 1964; 159:257–282.

    Article  CAS  PubMed  Google Scholar 

  • Picker LJ, EC Butcher. Physiological and molecular mechanisms of lymphocyte homing. Annu Rev Immunol 1992; 10:561–581.

    Article  CAS  PubMed  Google Scholar 

  • Mackay CR, Marston WL, Dudler L. Naive and memory T-cells show distinct pathways of lymphocyte recirculation. J Exp Med 1990; 171:801–817.

    Article  CAS  PubMed  Google Scholar 

  • Harris NL, Watt V, Ronchese F et al. Differential T-cell function and fate in lymph node and nonlymphoid tissues. J Exp Med 2002; 195(3):317–326.

    Article  CAS  PubMed  Google Scholar 

  • Xu RH, Fang M, Klein-Szanto A et al. CD8+ T-cells are gatekeepers of the lymph node draining the site of viral infection. Proc Natl Acad Sci USA 26; 104(26)2007:10992–10997.

    Article  CAS  Google Scholar 

  • Veazey RS, Rosenzweig M, Shvetz DE et al. Characterization of gut-associated lymphoid tissue (GALT) of normal Rhesus macaques. Clin Immunol Immunopath 1997; 82(3):230–242.

    Article  CAS  Google Scholar 

  • Veazey RS, DeMaria M, Chalifoux LV et al. Gastrointestinal tract as a major site of CD4+ T-cell depletion and viral replication in SIV infection. Science 1998; 280:427–431.

    Article  CAS  PubMed  Google Scholar 

  • Li Q, Duan L, Estes JD et al. Peak SIV replication in resting memory CD4+ T-cells depletes gut lamina propria CD4+ T-cells. Nature 2005; 434:1148–1152.

    CAS  PubMed  Google Scholar 

  • Mattapallil JJ, Douek DC, Hill B et al. Massive infection and loss of memory CD4+ T-cells in multiple tissues during acute SIV infection. Nature 2005; 434:1093–1097.

    Article  CAS  PubMed  Google Scholar 

  • Mehandru S, Poles MA, Tenner-Racz K et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T-lymphocytes from effector sites in the gastrointestinal tract. J Exp Med 2004; 200:761–770.

    Article  CAS  PubMed  Google Scholar 

  • Douek DC, Picker LJ, Koup RA. T-cell dynamics in HIV-1 infection. Annu Rev Immunol 2003; 21:265–304.

    Article  CAS  PubMed  Google Scholar 

  • Lundqvist C, Parker CM, Cepek KL et al. Distinct structural and functional epitopes of the αEß7 integrin. Eur J Immunol 1994; 24:2832–2841.

    Article  Google Scholar 

  • Cepek KL, Parker CM, Madara JL et al. Integrin αEß7 mediates adhesion of T-lymphocytes to epithelial cells. J Immunol 1993; 150:3459–3470.

    CAS  PubMed  Google Scholar 

  • Grossman Z, Meier-Schellersheim M, Paul WE et al. Pathogenesis of HIV infection: what the virus spares is as important as what it destroys. Nat Med 2006; 12:289–295.

    Article  CAS  PubMed  Google Scholar 

  • Picker LJ, Hagen SI, Lum R et al. Insufficient production and tissue delivery of CD4+ memory T-cells in rapidly progressive simian immunodeficiency virus infection. J Exp Med 2004; 200:1299–1314.

    Article  CAS  PubMed  Google Scholar 

  • Nishimura YT, Igarashi A, Buckler-White C et al. Loss of naive cells accompanies memory CD4+ T-cell depletion during long-term progression to AIDS in Simian immunodeficiency virus-infected macaques. J Virol 2007; 81:893–902.

    Article  CAS  PubMed  Google Scholar 

  • Hellerstein MK, Hoh RA, Hanley MB et al. Subpopulations of long-lived and short-lived T-cells in advanced HIV-1 infection. J Clin Invest 2003; 112:956–966.

    CAS  PubMed  Google Scholar 

  • Brenchley JM, Schacker TW, Ruff LE et al. CD4+ T-cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 2004; 200:749–759.

    Article  CAS  PubMed  Google Scholar 

  • Stevceva L, Kelsall B, Nacsa J et al. Cervicovaginal lamina propria lymphocytes: phenotypic characterization and their importance in cytotoxic T-Lymphocyte responses to Simian Immunodeficiency Virus SIVmac251. J Virol 2002; 76(1):9–18.

    Article  CAS  PubMed  Google Scholar 

  • Veazey RS, Marx PA, Lackner AA. Vaginal CD4+ T-cells express high levels of CCR5 and are rapidly depleted in simian immunodeficiency virus infection. J Infect Dis 2003; 187(5):769–776.

    Article  CAS  PubMed  Google Scholar 

  • Poonia B, Wang X, Veazey RS. Distribution of simian immunodeficiency virus target cells in vaginal tissues of normal Rhesus macaques: implications for virus transmission. J Reprod Immunol 2006; 72(1–2):74–84.

    Article  CAS  PubMed  Google Scholar 

  • Ma Z, Lu FX, Torten M et al. The number and distribution of immune cells in the cervicovaginal mucosa remain constant throughout the menstrual cycle of Rhesus macaques. Clin Immunol 2001; 100:240–249.

    Article  CAS  PubMed  Google Scholar 

  • McChesney MB, Collins JR, Miller CJ. Mucosal phenotype of antiviral cytotoxic T-lymphocytes in the vaginal mucosa of SIV-infected Rhesus macaques. AIDS Res Hum Retrovir 1998; 14(1):S63–S66.

    PubMed  Google Scholar 

  • Weston SA, Parish CR. New fluorescent dyes for lymphocyte migration studies. Analysis by flow cytometry and fluorescence microscopy. J Immunol Methods 1990; 133:87–97.

    Article  CAS  PubMed  Google Scholar 

  • Clay CC, Rodrigues DS, Brignolo LL et al. Chemokine networks and in vivo T-lymphocyte trafficking in non-human primates. J Immunol Methods 2004; 293:23–42.

    Article  CAS  PubMed  Google Scholar 

  • Clay CC, Rodrigues DS, Harvey DJ et al. Distinct chemokine triggers and in vivo migratory paths of fluorescein dye-labeled T-lymphocytes in acutely Simian Immunodeficiency Virus SIVmac251-infected and uninfected macaques. J Virol 2005; 79(21):13759–13768.

    Article  CAS  PubMed  Google Scholar 

  • Allers K, Kunkel D, Moos V et al. Migration patterns of non-specifically activated versus nonactivated non-human primate T-lymphocytes: preferential homing of activated autologous CD8+ T-cells in the rectal mucosa. J Immunother 2008; 31(4):334–344.

    Article  PubMed  Google Scholar 

  • Ho DD, Neumann AU, Perelson AS et al. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 1995; 373(6510):123–126.

    Article  CAS  PubMed  Google Scholar 

  • Mohri H, Bonhoeffer S, Monard S et al. Rapid turnover of T-lymphocytes in SIV-infected Rhesus macaques. Science 1998; 279(5354):1223–1227.

    Article  CAS  PubMed  Google Scholar 

  • Terry NH, White RA. Flow cytometry after bromodeoxyuridine labeling to measure S and G2+M phase durations plus doubling times in vitro and in vivo. Nature Protocols 2006; 1:859–869.

    Article  CAS  PubMed  Google Scholar 

  • Bonhoeffer S, Mohri H, Ho D et al. Quantification of cell turnover kinetics using 5-Bromo-2′-deoxyuridine. J Immunol 2000; 164:5049–5054.

    CAS  PubMed  Google Scholar 

  • De Boer RJ, Hiroshi Mohri H, David D. Ho D et al. Turnover Rates of B-Cells, T-Cells and NK Cells in Simian Immunodeficiency virus-infected and uninfected Rhesus macaques. J Immunol 2003; 170:2479–2487.

    PubMed  Google Scholar 

  • Cicin-Šain L, Messaoudi I, Park B et al. Dramatic increase in naïve T-cell turnover is linked to loss of naïve T-cells from old primates. Proc Natl Acad Sci USA 2007; 104(50):19960–19965.

    Article  PubMed  Google Scholar 

  • Kaur A, Di Mascio M, Barabasz A et al. Dynamics of T-and B-Lymphocyte Turnover in a Natural Host of Simian Immunodeficiency Virus. J Virol 2008; 82:1084–1093.

    Article  CAS  PubMed  Google Scholar 

  • Picker LJ, Reed-Inderbitzin EF, Hagen SI et al. IL-15 induces CD4+ effector memory T-cell production and tissue emigration in non-human primates. J Clin Invest 2006; 116(6):1514–1524.

    Article  CAS  PubMed  Google Scholar 

  • Healy DL, Bacher J, Hodgen GD. A method of thymectomy in macaques. J Med Primatol 1983; 12(2):89–100.

    CAS  PubMed  Google Scholar 

  • Arron ST, Riberio RM, Gettie A et al. Impact of thymectomy on the peripheral T-cell pool in rhesus macaques before and after infection with simian immunodeficiency virus. Eur J Immunol 2005; 35(1):46–55.

    Article  CAS  PubMed  Google Scholar 

  • Borghans JA, Hazenberg MD, Miedema F. Limited role for the thymus in SIV pathogenesis Eur J Immunol 2005; 35(1):42–45.

    Article  CAS  PubMed  Google Scholar 

  • Schmitz JE, Simon MA, Kuroda MJ et al. A non-human primate model for the selective elimination of CD8+ lymphocytes using a mouse-human chimeric monoclonal antibody. Am J Phatol 1999; 154(6):1923–1932.

    CAS  Google Scholar 

  • Permar SR, Klumpp SA, Mansfield KG et al. Role of CD8(+) lymphocytes in control and clearance of measles virus infection of rhesus monkeys. J Virol 2003; 77(7):4396–4400.

    Article  CAS  PubMed  Google Scholar 

  • Grakoui A, Shoukry NH, Woollard DJ et al. HCV Persistence and Immune Evasion in the Absence of Memory T-Cell Help. Science 2003; 302(5645):659–662.

    Article  CAS  PubMed  Google Scholar 

  • Edghill-Smith Y, Golding H, Manischewitz J et al. Smallpox vaccine-induced antibodies are necessary and sufficient for protection against monkeypox virus. Nat Med 2005; 11(7):740–747.

    Article  CAS  PubMed  Google Scholar 

  • Matano T, Shibata R, Siemon C et al. Administration of an anti-CD8 monoclonal antibody interferes with the clearance of chimeric simian/human immunodeficiency virus during primary infections of rhesus macaques. J Virol 1998; 72(1):164–169.

    CAS  PubMed  Google Scholar 

  • Schmitz JE, Johnson RP, McClure HM et al. Effect of CD8+ lymphocyte depletion on virus containment after simian immunodeficiency virus SIVmac251 challenge of live attenuated SIVmac239delta3-vaccinated Rhesus macaques. J Virol 2005; 79:8131–8141.

    Article  CAS  PubMed  Google Scholar 

  • Vaccari M, Mattapllil J, Song K et al. Reduced protection from simian immunodeficiency virus SIVmac251 infection afforded by memory CD8+ T-cells induced by vaccination during CD4+ T-cell deficiency. J Virol 2008; 82(19):9629–9638.

    Article  CAS  PubMed  Google Scholar 

  • Mavilio D, Lombardo G, Kinter A et al. Characterization of CD56-/CD16+ natural killer (NK) cells: a highly dysfunctional NK subset expanded in HIV-infected viremic individuals. Proc Natl Acad Sci USA 2005; 102:2886–2891.

    Article  CAS  PubMed  Google Scholar 

  • Choi EI, Wang R, Peterson L et al. Use of an anti-CD16 antibody for in vivo depletion of natural killer cells in rhesus macaques. Immunology; 2008; 124(2):215–222.

    Article  CAS  PubMed  Google Scholar 

  • Choi EI, Reimann KA, Letvin NL. In vivo natural killer cell depletion during primary simian immunodeficiency virus infection in rhesus monkeys. J Virol 2008; 82(13):6758–6761.

    Article  CAS  PubMed  Google Scholar 

  • Shedlock DJ, Shen H. Requirement for CD4 T-cell help in generating functional CD8 T-cell memory. Science 2003; 300:337–339.

    Article  CAS  PubMed  Google Scholar 

  • Sun JC, Williams MA, Bevan MJ. CD4+ T-cells are required for the maintenance, not programming, of memory CD8+ T-cells after acute infection. Nat Immunol 2004; 5:927–933.

    Article  CAS  PubMed  Google Scholar 

  • Janessen EM, Lemmens EE, Wolfe T et al. CD4+ T-cells are required for secondary expansion and memory in CD8+ T-lymphocytes. Nature 2003; 178:3492–3504.

    Google Scholar 

  • Ho VT, Soiffer RJ. The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation. Blood 2001; 98:3192–3204.

    Article  CAS  PubMed  Google Scholar 

  • van Kooten C, Banchereau J. CD40-CD40 ligand. J Leukoc Biol 2000; 67(1):2–17.

    PubMed  Google Scholar 

  • Grewal IS, Flavell RA. CD40 and CD154 in cell-mediated immunity. Annu Rev Immunol 1998; 16:111–135.

    Article  CAS  PubMed  Google Scholar 

  • Melter M, Reinders ME, Sho M et al. Ligation of CD40 induces the expression of vascular endothelial growth factor by endothelial cells and monocytes and promotes angiogenesis in vivo. Blood 2000; 96:3801–3808.

    CAS  PubMed  Google Scholar 

  • Reinders ME, Sho M, Robertson SW et al. Proangiogenic function of CD40 ligand-CD40 interactions. J Immunol 2003; 171:1534–1541.

    CAS  PubMed  Google Scholar 

  • Waterhouse P, Penninger JM, Timms E et al. Lymphoproliferative disorders with early lethality in mice deficient in CTLA-4. Science 1995; 270(5238):985–988.

    Article  CAS  PubMed  Google Scholar 

  • Larsen CP, Elwood ET, Alexander DZ et al. Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways. Nature 1996; 381:434–438.

    Article  CAS  PubMed  Google Scholar 

  • Kirk AD, Harlan DM, Armstrong NN et al. CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates. Proc Natl Acad Sci USA 1997; 94:8789–8794.

    Article  CAS  PubMed  Google Scholar 

  • Garber DA, Guido Silvestri G, Barry AP et al. Blockade of T-cell costimulation reveals interrelated actions of CD4+ and CD8+ T-cells in control of SIV replication. J Clin Invest 2004; 113(6):836–845.

    CAS  PubMed  Google Scholar 

  • Cecchinato V, Tryniszewska E, Ma ZM et al. Immune activation driven by CTLA-4 blockade augments viral replication at mucosal sites in simian immunodeficiency virus infection. J Immunol 2008; 180:5439–5447.

    CAS  PubMed  Google Scholar 

  • Mellor AL, Munn DH. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 2004; 4:762–774.

    Article  CAS  PubMed  Google Scholar 

  • Kovanen PE, Leonard WJ. Cytokines and immunodeficiency diseases: critical roles of the gamma (c)-dependent cytokines interleukins 2, 4, 7, 9, 15 and 21 and their signaling pathways. Immunol Rev 2004; 202:67–83.

    Article  CAS  PubMed  Google Scholar 

  • Alpdogan O, van den Brink MR. IL-7 and IL-15: therapeutic cytokines for immunodeficiency. Trends Immunol 2005; 26:56–64.

    Article  CAS  PubMed  Google Scholar 

  • Fry TJ, Moniuszko M, Creekmore S et al. IL-7 therapy dramatically alters peripheral T-cell homeostasis in normal and SIV-infected non-human primates. Blood 2003; 101:2294–2299.

    Article  CAS  PubMed  Google Scholar 

  • Malek TR, Bayer AL. Tolerance, not immunity, crucially depends on IL-2. Nat Rev Immunol 2004; 4:665–674.

    Article  CAS  PubMed  Google Scholar 

  • Khaled AR, Durum SK. Lymphocide: cytokines and the control of lymphoid homeostasis. Nat Rev Immunol 2002; 2:817–830.

    Article  CAS  PubMed  Google Scholar 

  • Tryniszewska E, Nacsa J, Lewis MG et al. Vaccination of macaques with long-standing SIVmac251 infection lowers the viral set point after cessation of antiretroviral therapy. J Immunol 2002; 169(9):5347–5357.

    PubMed  Google Scholar 

  • Nacsa J, Edghill-Smith Y, Tsai WP et al. Contrasting effects of low-dose IL-2 on vaccine-boosted simian immunodeficiency virus (SIV)-specific CD4+ and CD8+ T-cells in macaques chronically infected with SIVmac251. J Immunol 2005; 174(4):1913–1921.

    CAS  PubMed  Google Scholar 

  • Barouch DH, Letvin NL, Seder RA. Expression kinetics of the interleukin-2/immunoglobulin (IL-2/Ig) plasmid cytokine adjuvant. Vaccine 2004; 22(23–24):3092–3097.

    Article  CAS  PubMed  Google Scholar 

  • Villinger F, Miller R, Mori K et al. IL-15 is superior to IL-2 in the generation of long-lived antigen specific memory CD4 and CD8 T-cells in rhesus macaques. Vaccine 2004; 22(25-26):3510–3521.

    Article  CAS  PubMed  Google Scholar 

  • von Freeden-Jeffry U, Vieira P, Lucian LA et al. Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J Exp Med 1995; 181:1519–1526.

    Article  Google Scholar 

  • Peschon JJ, Morrissey PJ, Grabstein KH et al. Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J Exp Med 1994; 180:1955–1960.

    Article  CAS  PubMed  Google Scholar 

  • Kieper WC, Tan JT, B. Bondi-Boyd B et al. Overexpression of interleukin (IL)-7 leads to IL-15-independent generation of memory phenotype CD8+ T-cells. J Exp Med 2002; 195:1533–1539.

    Article  CAS  PubMed  Google Scholar 

  • Schluns KS, Kieper WC, Jameson SC et al. Interleukin-7 mediates the homeostasis of naive and memory CD8 T-cells in vivo. Nat Immunol 2000; 1:426–432.

    Article  CAS  PubMed  Google Scholar 

  • Schluns KS, Lefrancois L. Cytokine control of memory T-cell development and survival. Nat Rev Immunol 2003; 3:269–279.

    Article  CAS  PubMed  Google Scholar 

  • Lantz O, Grandjean I, Matzinger P et al. Gamma chain required for naive CD4+ T-cell survival but not for antigen proliferation. Nat Immunol 2000; 1:54–58.

    Article  CAS  PubMed  Google Scholar 

  • Tan JT, Dudl E, LeRoy E et al. IL-7 is critical for homeostatic proliferation and survival of naive T-cells. Proc Natl Acad Sci USA 2001; 98:8732–8737.

    Article  CAS  PubMed  Google Scholar 

  • Wiryana P, Bui T, Faltynek CR et al. Augmentation of cell-mediated immunotherapy against herpes simplex virus by interleukins: comparison of in vivo effects of IL-2 and IL-7 on adoptively transferred T-cells. Vaccine 1997; 15:561–563.

    Article  CAS  PubMed  Google Scholar 

  • Moniuszko M, Fry T, Tsai WP et al. Recombinant interleukin-7 induces proliferation of naive macaque CD4+ and CD8+ T-Cells in vivo. J Virol 2004; 78(18):9740–9749.

    Article  CAS  PubMed  Google Scholar 

  • Dereuddre-Bosquet N, Vaslin B, Delache B et al. Rapid modifications of peripheral T-cell subsets that express CD127 in macaques treated with recombinant IL-7. J Med Primatol 2007; 36(4–5):228–237.

    Article  CAS  PubMed  Google Scholar 

  • Villinger F, Miller R, Mori K et al. IL-15 is superior to IL-2 in the generation of long-lived antigen specific memory CD4 and CD8 T-cells in Rhesus macaques. Vaccine 2004; 22:3510–3521.

    Article  CAS  PubMed  Google Scholar 

  • Beq S, Nugeyre MT, Fang RHT et al. IL-7 induces immunological improvement in SIV-infected rhesus macaques under antiviral therapy. J Immunol 2006; 176:914–922.

    CAS  PubMed  Google Scholar 

  • Mueller YM, Do DH, Altork SR et al. IL-15 treatment during acute simian immunodeficiency virus (SIV) infection increases viral set point and accelerates disease progression despite the induction of stronger SIV-specific CD8+ T-cell responses. J Immunol 2008; 180(1):350–360.

    CAS  PubMed  Google Scholar 

  • Demberg T, Boyer JD, Malkevich N et al. Sequential priming with simian immunodeficiency virus (SIV) DNA vaccines, with or without encoded cytokines and a replicating adenovirus-SIV recombinant followed by protein boosting does not control a pathogenic SIVmac251 mucosal challenge. J Virol 2008; 82(21):10911–10921.

    Article  CAS  PubMed  Google Scholar 

  • Hryniewicz A, Price DA, Moniuszko M et al. Interleukin-15 but not interleukin-7 abrogates vaccine-induced decrease in virus level in simian immunodeficiency virusmac 251-infected macaques. J Immunol 2007; 178:3492–3504.

    CAS  PubMed  Google Scholar 

  • Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol 2004; 5:133–139.

    Article  CAS  PubMed  Google Scholar 

  • Miller RA, Garcia G, Kirk CJ et al. Early activation defects in T-lymphocytes from aged mice. Immunol Rev 1997; 160:79–90.

    Article  CAS  PubMed  Google Scholar 

  • Eisenbraun M, Tamir A, Miller RA. Altered composition of the immunological synapse in an anergic, age-dependent memory T-cell subset. J Immunol 2000; 164:6105–6112.

    CAS  PubMed  Google Scholar 

  • Flajnik MF, Kasai M. Comparative genomics of the MHC: glimpses into the evolution of the adaptive immune system. Immunity 2001; 15:351–362.

    Article  CAS  PubMed  Google Scholar 

  • Murphy WJ, Stanyon R, O’Brien SJ. Evolution of mammalian genome organization inferred from comparative gene mapping. Genome Biol 2001; 2:0005.1–0005.8.

    Article  Google Scholar 

  • Roth GS, Mattison JA, Ottinger MA et al. Aging in rhesus monkeys: relevance to human health Interventions. Science 2004; 305(5689); 1423–1426.

    Article  CAS  PubMed  Google Scholar 

  • Messaoudi I, Warner J, Fischer M et al. Delay of T-cell senescence by caloric restriction in aged long-lived non-human primates. Proc Natl Acad Sci USA 2006; 103:19448–19453.

    Article  CAS  PubMed  Google Scholar 

  • Douek DC, McFarland RD, Keiser PH et al. Changes in thymic function with age and during the treatment of HIV infection. Nature 1998; 396:690–695.

    Article  CAS  PubMed  Google Scholar 

  • McFarland RD, Douek DC, Koup RA et al. Identification of a human recent thymic emigrant phenotype. Proc Natl Acad Sci USA 2000; 97:4215–4220.

    Article  CAS  PubMed  Google Scholar 

  • Jankovié V, Messaoudi I, Nikolich-žugich J. Phenotypic and functional T-cell aging in Rhesus macaques (Macaca mulatta): differential behavior of CD4 and CD8 subsets. Blood 2003; 102(9):3244–3251.

    Article  CAS  Google Scholar