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Memory T Cells in Rhesus Macaques

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Memory T Cells

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 684))

Abstract

The Rhesus macaque (Macaca mulatta) is one of the best studied species of Old World monkeys. DNA sequencing of the entire Rhesus macaque genome, completed in 2007, has demonstrated that humans and macaques share about 93% of their nucleotide sequence. Rhesus macaques have been widely used for medical research including drug testing, neurology, behavioral and cognitive science, reproduction, xenotransplantation and genetics. Because of the Rhesus macaque’s sensitivity to bacteria, parasites and viruses that cause similar disease in humans, these animals represent an excellent model to study infectious diseases. The recent pandemic of HIV and the discovery of SIV, a lentivirus genetically related to HIV Type 1 that causes AIDS in Rhesus macaques, have prompted the development of reagents that can be used to study innate and adaptive immune responses in macaques at the single cell level. This review will focus on the distribution of memory cells in the different immunologic compartments of Rhesus macaques. In addition, the strategies available to manipulate memory cells in Rhesus macaques to understand their trafficking and function will be discussed. Emphasis is placed on studies of memory cells in macaques infected with SIV because many studies are available. Lastly, we highlight the usefulness of the Rhesus macaque model in studies related to the aging of the immune system.

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References

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

    Google Scholar 

  2. 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 

  3. 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 

  4. 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 

  5. 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 

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

    Article  CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  8. 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 

  9. 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 

  10. 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 

  11. 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 

  12. 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 

  13. 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 

  14. 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 

  15. 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 

  16. 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 

  17. 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 

  18. 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 

  19. 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 

  20. 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 

  21. 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 

  22. 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 

  23. 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 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  28. 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 

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

    Article  CAS  PubMed  Google Scholar 

  30. 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 

  31. 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 

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

    Article  CAS  Google Scholar 

  33. 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 

  34. 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 

  35. 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 

  36. 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 

  37. 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 

  38. 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 

  39. 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 

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

    Article  CAS  PubMed  Google Scholar 

  41. 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 

  42. 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 

  43. 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 

  44. 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 

  45. 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 

  46. 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 

  47. 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 

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

    Article  CAS  Google Scholar 

  49. 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 

  50. 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 

  51. 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 

  52. 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 

  53. 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 

  54. 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 

  55. 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 

  56. 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 

  57. 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 

  58. 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 

  59. 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 

  60. 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 

  61. 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 

  62. 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 

  63. 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 

  64. 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 

  65. 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 

  66. 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 

  67. 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 

  68. 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 

  69. 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 

  70. 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 

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

    Article  CAS  PubMed  Google Scholar 

  72. 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 

  73. 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 

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

    Article  CAS  PubMed  Google Scholar 

  75. 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 

  76. 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 

  77. 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 

  78. 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 

  79. 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 

  80. 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 

  81. 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 

  82. 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 

  83. 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 

  84. 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 

  85. 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 

  86. 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 

  87. 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 

  88. 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 

  89. 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 

  90. 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 

  91. 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 

  92. 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 

  93. 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 

  94. 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 

  95. 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 

  96. 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 

  97. 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 

  98. 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 

  99. 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 

  100. 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 

  101. 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 

  102. 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 

  103. 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 

  104. 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 

  105. 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 

  106. 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 

  107. 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 

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

    CAS  PubMed  Google Scholar 

  109. 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 

  110. 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 

  111. 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 

  112. 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 

  113. 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 

  114. 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 

  115. 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 

  116. 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 

  117. 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 

  118. 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 

  119. 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 

  120. 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 

  121. 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 

  122. 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 

  123. 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 

  124. 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 

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

    PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  127. 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 

  128. 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 

  129. 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 

  130. 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 

  131. 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 

  132. 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 

  133. 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 

  134. 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 

  135. 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 

  136. 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 

  137. 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 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  140. 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 

  141. 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 

  142. 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 

  143. 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 

  144. 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 

  145. 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 

  146. 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 

  147. 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 

  148. 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 

  149. 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 

  150. 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 

  151. 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 

  152. 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 

  153. 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 

  154. 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 

  155. 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 

  156. 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 

  157. 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 

  158. 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 

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

    Article  CAS  PubMed  Google Scholar 

  160. 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 

  161. 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 

  162. 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 

  163. 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 

  164. 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 

  165. 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 

  166. 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 

  167. 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 

  168. 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 

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Vaccari, M., Franchini, G. (2010). Memory T Cells in Rhesus Macaques. In: Zanetti, M., Schoenberger, S.P. (eds) Memory T Cells. Advances in Experimental Medicine and Biology, vol 684. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6451-9_10

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