Advertisement

The Role of Inflammation in the Generation and Maintenance of Memory T Cells

  • Noah S. Butler
  • John T. Harty
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 684)

Abstract

Following infection or vaccination, antigen-specific T cells undergo enormous expansion in numbers and differentiate into effector cells that control infection and modulate other aspects of innate and adaptive immunity. The effector T-cell expansion phase is followed by an abrupt period of contraction, during which 90–95% of antigen-specific T cells are eliminated. The surviving pool of T cells subsequently differentiates into long-lived memory populations that can persist for the life of the host and mediate enhanced protective immunity following pathogen re-infection. The generation and maintenance of memory T-cell populations are influenced by a multitude of factors, including inflammatory cytokines that can act on T cells at various points during their differentiation. Herein, we discuss our current understanding of how inflammation shapes not only the quantity and quality of memory T cells, but also the rate at which functional memory T-cell populations develop.

Keywords

Contraction Phase LCMV Infection Listeria Monocytogenes Infection Proliferative Expansion Follow LCMV Infection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Sprent J, Cho JH, Boyman O et al. T-cell homeostasis. Immunol Cell Biol 2008; 86(4):312–319.PubMedCrossRefGoogle Scholar
  2. 2.
    Castellino F, Germain RN. Cooperation between CD4+ and CD8+ T-cells: when, where and how. Annu Rev Immunol 2006; 24:519–540.PubMedCrossRefGoogle Scholar
  3. 3.
    Heath WR, Carbone FR. Cross-presentation, dendritic cells, tolerance and immunity. Annu Rev Immunol 2001; 19:47–64.PubMedCrossRefGoogle Scholar
  4. 4.
    Schwab SR, Cyster JG. Finding a way out: lymphocyte egress from lymphoid organs. Nat Immunol 2007; 8(12):1295–1301.PubMedCrossRefGoogle Scholar
  5. 5.
    Badovinac VP, Harty JT. Programming, demarcating and manipulating CD8+ T-cell memory. Immunol Rev 2006; 211:67–80.PubMedCrossRefGoogle Scholar
  6. 6.
    Kaech SM, Wherry EJ, Ahmed R. Effector and memory T-cell differentiation: implications for vaccine development. Nat Rev Immunol 2002; 2(4):251–262.PubMedCrossRefGoogle Scholar
  7. 7.
    Badovinac VP, Harty JT. CD8(+) T-cell homeostasis after infection: setting the ‘curve’. Microbes Infect 2002; 4(4):441–447.PubMedCrossRefGoogle Scholar
  8. 8.
    Badovinac VP, Porter BB, Harty JT. Programmed contraction of CD8(+) T-cells after infection. Nat Immunol 2002; 3(7):619–626.PubMedGoogle Scholar
  9. 9.
    Kaech SM, Ahmed R. Memory CD8+ T-cell differentiation: initial antigen encounter triggers a developmental program in naive cells. Nat Immunol 2001; 2(5):415–422.PubMedGoogle Scholar
  10. 10.
    Mercado R, Vijh S, Allen SE et al. Early programming of T-cell populations responding to bacterial infection. J Immunol 2000; 165(12):6833–6839.PubMedGoogle Scholar
  11. 11.
    Masopust D, Vezys V, Marzo AL et al. Preferential localization of effector memory cells in nonlymphoid tissue. Science 2001; 291(5512):2413–2417.PubMedCrossRefGoogle Scholar
  12. 12.
    Blattman JN, Antia R, Sourdive DJ et al. Estimating the precursor frequency of naive antigen-specific CD8 T-cells. J Exp Med 2002; 195(5):657–664.PubMedCrossRefGoogle Scholar
  13. 13.
    Casrouge A, Beaudoing E, Dalle S et al. Size estimate of the alpha beta TCR repertoire of naive mouse splenocytes. J Immunol 2000; 164(11):5782–5787.PubMedGoogle Scholar
  14. 14.
    Moon JJ, Chu HH, Pepper M et al. Naive CD4(+) T-cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude. Immunity 2007; 27(2):203–213.PubMedCrossRefGoogle Scholar
  15. 15.
    Hou S, Hyland L, Ryan KW et al. Virus-specific CD8+ T-cell memory determined by clonal burst size. Nature 1994; 369(6482):652–654.PubMedCrossRefGoogle Scholar
  16. 16.
    Haring JS, Badovinac VP, Harty JT. Inflaming the CD8+ T-cell response. Immunity 2006; 25(1):19–29.PubMedCrossRefGoogle Scholar
  17. 17.
    Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells. Annu Rev Immunol 2003; 21:685–711.PubMedCrossRefGoogle Scholar
  18. 18.
    Marrack P, Kappler J, Mitchell T. Type I interferons keep activated T-cells alive. J Exp Med 1999; 189(3):521–530.PubMedCrossRefGoogle Scholar
  19. 19.
    Curtsinger JM, Schmidt CS, Mondino A et al. Inflammatory cytokines provide a third signal for activation of naive CD4+ and CD8+ T-cells. J Immunol 1999; 162(6):3256–3262.PubMedGoogle Scholar
  20. 20.
    Curtsinger JM, Valenzuela JO, Agarwal P et al. Type I IFNs provide a third signal to CD8 T-cells to stimulate clonal expansion and differentiation. J Immunol 2005; 174(8):4465–4469.PubMedGoogle Scholar
  21. 21.
    Schmidt CS, Mescher MF. Adjuvant effect of IL-12: conversion of peptide antigen administration from tolerizing to immunizing for CD8+ T-cells in vivo. J Immunol 1999; 163(5):2561–2567.PubMedGoogle Scholar
  22. 22.
    Havenar-Daughton C, Kolumam GA, Murali-Krishna K. Cutting Edge: The direct action of type I IFN on CD4 T-cells is critical for sustaining clonal expansion in response to a viral but not a bacterial infection. J Immunol 2006; 176(6):3315–3319.PubMedGoogle Scholar
  23. 23.
    Aichele P, Unsoeld H, Koschella M et al. CD8 T-cells specific for lymphocytic choriomeningitis virus require type I IFN receptor for clonal expansion. J Immunol 2006; 176(8):4525–4529.PubMedGoogle Scholar
  24. 24.
    Curtsinger JM, Johnson CM, Mescher MF. CD8 T-cell clonal expansion and development of effector function require prolonged exposure to antigen, costimulation and signal 3 cytokine. J Immunol 2003; 171(10):5165–5171.PubMedGoogle Scholar
  25. 25.
    Kolumam GA, Thomas S, Thompson LJ et al. Type I interferons act directly on CD8 T-cells to allow clonal expansion and memory formation in response to viral infection. J Exp Med 2005; 202(5):637–650.PubMedCrossRefGoogle Scholar
  26. 26.
    Sercan O, Hammerling GJ, Arnold B et al. Innate immune cells contribute to the IFN-gamma-dependent regulation of antigen-specific CD8+ T-cell homeostasis. J Immunol 2006; 176(2):735–739.Google Scholar
  27. 27.
    Whitmire JK, Tan JT, Whitton JL. Interferon-gamma acts directly on CD8+ T-cells to increase their abundance during virus infection. J Exp Med 2005; 201(7):1053–1059.PubMedCrossRefGoogle Scholar
  28. 28.
    Cousens LP, Peterson R, Hsu S et al. Two roads diverged: interferon alpha/beta-and interleukin 12-mediated pathways in promoting T-cell interferon gamma responses during viral infection. J Exp Med 1999; 189(8):1315–1328.PubMedCrossRefGoogle Scholar
  29. 29.
    Ou R, Zhou S, Huang L et al. Critical role for alpha/beta and gamma interferons in persistence of lymphocytic choriomeningitis virus by clonal exhaustion of cytotoxic T-cells. J Virol 2001; 75(18):8407–8423.PubMedCrossRefGoogle Scholar
  30. 30.
    Pearce EL, Shen H. Generation of CD8 T-cell memory is regulated by IL-12. J Immunol 2007; 179(4):2074–2081.PubMedGoogle Scholar
  31. 31.
    Cousens LP, Orange JS, Su HC et al. Interferon-alpha/beta inhibition of interleukin 12 and interferon-gamma production in vitro and endogenously during viral infection. Proc Natl Acad Sci USA 1997; 94(2):634–639.PubMedCrossRefGoogle Scholar
  32. 32.
    Thomas S, Kolumam GA, Murali-Krishna K. Antigen presentation by nonhemopoietic cells amplifies clonal expansion of effector CD8 T-cells in a pathogen-specific manner. J Immunol 2007; 178(9):5802–5811.PubMedGoogle Scholar
  33. 33.
    Thompson LJ, Kolumam GA, Thomas S et al. Innate inflammatory signals induced by various pathogens differentially dictate the IFN-I dependence of CD8 T-cells for clonal expansion and memory formation. J Immunol 2006; 177(3):1746–1754.PubMedGoogle Scholar
  34. 34.
    Way SS, Havenar-Daughton C, Kolumam GA et al. IL-12 and type-I IFN synergize for IFN-gamma production by CD4 T-cells, whereas neither are required for IFN-gamma production by CD8 T-cells after Listeria monocytogenes infection. J Immunol 2007; 178(7):4498–4505.PubMedGoogle Scholar
  35. 35.
    Valenzuela JO, Hammerbeck CD, Mescher MF. Cutting edge: Bcl-3 up-regulation by signal 3 cytokine (IL-12) prolongs survival of antigen-activated CD8 T-cells. J Immunol 2005; 174(2):600–604.PubMedGoogle Scholar
  36. 36.
    Mitchell TC, Hildeman D, Kedl RM et al. Immunological adjuvants promote activated T-cell survival via induction of Bcl-3. Nat Immunol 2001; 2(5):397–402.PubMedGoogle Scholar
  37. 37.
    Wojciechowski S, Tripathi P, Bourdeau T et al. Bim/Bcl-2 balance is critical for maintaining naive and memory T-cell homeostasis. J Exp Med 2007; 204(7):1665–1675.PubMedGoogle Scholar
  38. 38.
    Corbin GA, Harty JT. Duration of infection and antigen display have minimal influence on the kinetics of the CD4+ T-cell response to Listeria monocytogenes infection. J Immunol 2004; 173(9):5679–5687.PubMedGoogle Scholar
  39. 39.
    Fuller MJ, Khanolkar A, Tebo AE et al. Maintenance, loss and resurgence of T-cell responses during acute, protracted and chronic viral infections. J Immunol 2004; 172(7):4204–4214.PubMedGoogle Scholar
  40. 40.
    Wherry EJ, Teichgraber V, Becker TC et al. Lineage relationship and protective immunity of memory CD8 T-cell subsets. Nat Immunol 2003; 4(3):225–234.PubMedCrossRefGoogle Scholar
  41. 41.
    Badovinac VP, Tvinnereim AR, Harty JT. Regulation of antigen-specific CD8+ T-cell homeostasis by perforin and interferon-gamma. Science 2000; 290(5495):1354–1358.PubMedCrossRefGoogle Scholar
  42. 42.
    Tewari K, Nakayama Y, Suresh M. Role of direct effects of IFN-gamma on T-cells in the regulation of CD8 T-cell homeostasis. J Immunol 2007; 179(4):2115–2125.PubMedGoogle Scholar
  43. 43.
    Whitmire JK, Eam B, Benning N et al. Direct interferon-gamma signaling dramatically enhances CD4+ and CD8+ T-cell memory. J Immunol 2007; 179(2):1190–1197.PubMedGoogle Scholar
  44. 44.
    Badovinac VP, Porter BB, Harty JT. CD8+ T-cell contraction is controlled by early inflammation. Nat Immunol 2004; 5(8):809–817.PubMedCrossRefGoogle Scholar
  45. 45.
    Haring JS, Harty JT. Aberrant contraction of antigen-specific CD4 T-cells after infection in the absence of gamma interferon or its receptor. Infect Immun 2006; 74(11):6252–6263.PubMedCrossRefGoogle Scholar
  46. 46.
    Haring JS, Corbin GA, Harty JT. Dynamic regulation of IFN-gamma signaling in antigen-specific CD8+ T-cells responding to infection. J Immunol 2005; 174(11):6791–6802.PubMedGoogle Scholar
  47. 47.
    Joshi NS, Cui W, Chandele A et al. Inflammation directs memory precursor and short-lived effector CD8(+) T-cell fates via the graded expression of T-bet transcription factor. Immunity 2007; 27(2):281–295.PubMedCrossRefGoogle Scholar
  48. 48.
    Intlekofer AM, Takemoto N, Kao C et al. Requirement for T-bet in the aberrant differentiation of unhelped memory CD8+ T-cells. J Exp Med 2007; 204(9):2015–2021.PubMedCrossRefGoogle Scholar
  49. 49.
    Nguyen LT, McKall-Faienza K, Zakarian A et al. TNF receptor 1 (TNFR1) and CD95 are not required for T-cell deletion after virus infection but contribute to peptide-induced deletion under limited conditions. Eur J Immunol 2000; 30(2):683–688.PubMedCrossRefGoogle Scholar
  50. 50.
    Reich A, Korner H, Sedgwick JD et al. Immune down-regulation and peripheral deletion of CD8 T-cells does not require TNF receptor-ligand interactions nor CD95 (Fas, APO-1). Eur J Immunol 2000; 30(2):678–682.PubMedCrossRefGoogle Scholar
  51. 51.
    Huster KM, Busch V, Schiemann M et al. Selective expression of IL-7 receptor on memory T-cells identifies early CD40L-dependent generation of distinct CD8+ memory T-cell subsets. Proc Natl Acad Sci USA 2004; 101(15):5610–5615.PubMedCrossRefGoogle Scholar
  52. 52.
    Kaech SM, Tan JT, Wherry EJ et al. Selective expression of the interleukin 7 receptor identifies effector CD8 T-cells that give rise to long-lived memory cells. Nat Immunol 2003; 4(12):1191–1198.PubMedCrossRefGoogle Scholar
  53. 53.
    Haring JS, Jing X, Bollenbacher-Reilley J et al. Constitutive expression of IL-7 receptor alpha does not support increased expansion or prevent contraction of antigen-specific CD4 or CD8 T-cells following Listeria monocytogenes infection. J Immunol 2008; 180(5):2855–2862.PubMedGoogle Scholar
  54. 54.
    Hand TW, Morre M, Kaech SM. Expression of IL-7 receptor alpha is necessary but not sufficient for the formation of memory CD8 T-cells during viral infection. Proc Natl Acad Sci USA 2007; 104(28):11730–11735.PubMedCrossRefGoogle Scholar
  55. 55.
    Badovinac VP, Messingham KA, Jabbari A et al. Accelerated CD8+ T-cell memory and prime-boost response after dendritic-cell vaccination. Nat Med 2005; 11(7):748–756.PubMedCrossRefGoogle Scholar
  56. 56.
    Lacombe MH, Hardy MP, Rooney J et al. IL-7 receptor expression levels do not identify CD8+ memory T-lymphocyte precursors following peptide immunization. J Immunol 2005; 175(7):4400–4407.PubMedGoogle Scholar
  57. 57.
    Hildeman DA, Zhu Y, Mitchell TC et al. Activated T-cell death in vivo mediated by proapoptotic bcl-2 family member bim. Immunity 2002; 16(6):759–767.PubMedCrossRefGoogle Scholar
  58. 58.
    Pellegrini M, Belz G, Bouillet P et al. Shutdown of an acute T-cell immune response to viral infection is mediated by the proapoptotic Bcl-2 homology 3-only protein Bim. Proc Natl Acad Sci USA 2003; 100(24):14175–14180.PubMedCrossRefGoogle Scholar
  59. 59.
    Grayson JM, Weant AE, Holbrook BC et al. Role of Bim in regulating CD8+ T-cell responses during chronic viral infection. J Virol 2006; 80(17):8627–8638.PubMedCrossRefGoogle Scholar
  60. 60.
    Hughes PD, Belz GT, Fortner KA et al. Apoptosis regulators Fas and Bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity. Immunity 2008; 28(2):197–205.CrossRefGoogle Scholar
  61. 61.
    Weant AE, Michalek RD, Khan IU et al. Apoptosis regulators Bim and Fas function concurrently to control autoimmunity and CD8+ T-cell contraction. Immunity 2008; 28(2):218–230.PubMedCrossRefGoogle Scholar
  62. 62.
    Curtsinger JM, Lins DC, Mescher MF. Signal 3 determines tolerance versus full activation of naive CD8 T-cells: dissociating proliferation and development of effector function. J Exp Med 2003; 197(9):1141–1151.PubMedCrossRefGoogle Scholar
  63. 63.
    Badovinac VP, Harty JT. Intracellular staining for TNF and IFN-gamma detects different frequencies of antigen-specific CD8(+) T-cells. J Immunol Methods 2000; 238(1–2):107–117.PubMedCrossRefGoogle Scholar
  64. 64.
    Altman JD, Moss PA, Goulder PJ et al. Phenotypic analysis of antigen-specific T-lymphocytes. Science 1996; 274(5284):94–96.PubMedCrossRefGoogle Scholar
  65. 65.
    Badovinac VP, Harty JT. Manipulating the rate of memory CD8+ T-cell generation after acute infection. J Immunol 2007; 179(1):53–63.PubMedGoogle Scholar
  66. 66.
    Williams MA, Ravkov EV, Bevan MJ. Rapid culling of the CD4+ T-cell repertoire in the transition from effector to memory. Immunity 2008; 28(4):533–545.PubMedCrossRefGoogle Scholar
  67. 67.
    Iwai Y, Hemmi H, Mizenina O et al. An IFN-gamma-IL-18 signaling loop accelerates memory CD8+ T-cell proliferation. PLoS ONE 2008; 3(6):e2404.PubMedCrossRefGoogle Scholar
  68. 68.
    Northrop JK, Wells AD, Shen H. Cutting edge: chromatin remodeling as a molecular basis for the enhanced functionality of memory CD8 T-cells. J Immunol 2008; 181(2):865–868.PubMedGoogle Scholar
  69. 69.
    Lau LL, Jamieson BD, Somasundaram T et al. Cytotoxic T-cell memory without antigen. Nature 1994; 369(6482):648–652.PubMedCrossRefGoogle Scholar
  70. 70.
    Swain SL, Hu H, Huston G. Class II-independent generation of CD4 memory T-cells from effectors. Science 1999; 286(5443):1381–1383.PubMedCrossRefGoogle Scholar
  71. 71.
    Murali-Krishna K, Lau LL, Sambhara S et al. Persistence of memory CD8 T-cells in MHC class I-deficient mice. Science 1999; 286(5443):1377–1381.PubMedCrossRefGoogle Scholar
  72. 72.
    Goldrath AW, Sivakumar PV, Glaccum M et al. Cytokine requirements for acute and Basal homeostatic proliferation of naive and memory CD8+ T-cells. J Exp Med 2002; 195(12):1515–1522.CrossRefGoogle Scholar
  73. 73.
    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(5):426–432.PubMedCrossRefGoogle Scholar
  74. 74.
    Schluns KS, Lefrancois L. Cytokine control of memory T-cell development and survival. Nat Rev Immunol 2003; 3(4):269–279.PubMedCrossRefGoogle Scholar
  75. 75.
    Schluns KS, Williams K, Ma A et al. Cutting edge: requirement for IL-15 in the generation of primary and memory antigen-specific CD8 T-cells. J Immunol 2002; 168(10):4827–4831.PubMedGoogle Scholar
  76. 76.
    Becker TC, Wherry EJ, Boone D et al. Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T-cells. J Exp Med 2002; 195(12):1541–1548.PubMedCrossRefGoogle Scholar
  77. 77.
    Tan JT, Ernst B, Kieper WC et al. Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells. J Exp Med 2002; 195(12):1523–1532.PubMedCrossRefGoogle Scholar
  78. 78.
    Cush SS, Anderson KM, Ravneberg DH et al. Memory generation and maintenance of CD8+ T-cell function during viral persistence. J Immunol 2007; 179(1):141–153.PubMedGoogle Scholar
  79. 79.
    Wherry EJ, Blattman JN, Murali-Krishna K et al. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J Virol 2003; 77(8):4911–4927.PubMedCrossRefGoogle Scholar
  80. 80.
    Moskophidis D, Lechner F, Pircher H et al. Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T-cells. Nature 1993; 362(6422):758–761.PubMedCrossRefGoogle Scholar
  81. 81.
    Fuller MJ, Hildeman DA, Sabbaj S et al. Cutting edge: emergence of CD127high functionally competent memory T-cells is compromised by high viral loads and inadequate T-cell help. J Immunol 2005; 174(10):5926–5930.PubMedGoogle Scholar
  82. 82.
    Lang KS, Recher M, Navarini AA et al. Inverse correlation between IL-7 receptor expression and CD8 T-cell exhaustion during persistent antigen stimulation. Eur J Immunol 2005; 35(3):738–745.CrossRefGoogle Scholar
  83. 83.
    Wherry EJ, Barber DL, Kaech SM et al. Antigen-independent memory CD8 T-cells do not develop during chronic viral infection. Proc Natl Acad Sci USA 2004; 101(45):16004–16009.PubMedCrossRefGoogle Scholar
  84. 84.
    Barber DL, Wherry EJ, Masopust D et al. Restoring function in exhausted CD8 T-cells during chronic viral infection. Nature 2006; 439(7077):682–687.PubMedCrossRefGoogle Scholar
  85. 85.
    Decrion AZ, Dichamp I, Varin A et al. HIV and inflammation. Curr HIV Res 2005; 3(3):243–259.PubMedCrossRefGoogle Scholar
  86. 86.
    Leavey JK, Tarleton RL. Cutting edge: dysfunctional CD8+ T-cells reside in nonlymphoid tissues during chronic Trypanosoma cruzi infection. J Immunol 2003; 170(5):2264–2268.Google Scholar
  87. 87.
    Maini MK, Boni C, Lee CK et al. The role of virus-specific CD8(+) cells in liver damage and viral control during persistent hepatitis B virus infection. J Exp Med 2000; 191(8):1269–1280.PubMedCrossRefGoogle Scholar
  88. 88.
    Dudani R, Murali-Krishna K, Krishnan L et al. IFN-gamma induces the erosion of preexisting CD8 T-cell memory during infection with a heterologous intracellular bacterium. J Immunol 2008; 181(3):1700–1709.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science +Business Media 2010

Authors and Affiliations

  1. 1.Department of MicrobiologyUniversity of IowaIowa CityUSA

Personalised recommendations