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Longevity of T-Cell Memory following Acute Viral Infection

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Memory T Cells

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

Abstract

Investigation of T-cell-mediated immunity following acute viral infection represents an area of research with broad implications for both fundamental immunology research as well as vaccine development. Here, we review techniques that are used to assess T-cell memory including limiting dilution analysis, enzyme-linked immunospot (ELISPOT) assays, intracellular cytokine staining (ICCS) and peptide-MHC Class I tetramer staining. The durability of T-cell memory is explored in the context of several acute viral infections including vaccinia virus (VV), measles virus (MV) and yellow fever virus (YFV). Following acute infection, different virus-specific T-cell subpopulations exhibit distinct cytokine profiles and these profiles change over the course of infection. Differential regulation of the cytotoxic proteins, granzyme A, granzyme B and perforin are also observed in virus-specific T cells following infection. As a result of this work, we have gained a broader understanding of the kinetics and magnitude of antiviral T-cell immunity as well as new insight into the patterns of immunodominance and differential regulation of cytokines and cytotoxicity-associated molecules. This information may eventually lead to the generation of more effective vaccines that elicit T-cell memory with the optimal combination of functional characteristics required for providing protective immunity against infectious disease.

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References

  1. Masopust D, Vezys V, Wherry EJ et al. A brief history of CD8 T-cells. Eur J Immunol 2007; 37(Suppl 1):S103–110.

    Article  CAS  PubMed  Google Scholar 

  2. Mitchell GF, Miller JF. Immunological activity of thymus and thoracic-duct lymphocytes. Proc Natl Acad Sci USA 1968; 59(1):296–303.

    Article  CAS  PubMed  Google Scholar 

  3. Cerottini JC, Nordin AA, Brunner KT. Specific in vitro cytotoxicity of thymus-derived lymphocytes sensitized to alloantigens. Nature 1970; 228(5278):1308–1309.

    Article  CAS  PubMed  Google Scholar 

  4. Golstein P, Wigzell H, Blomgren H et al. Cells mediating specific in vitro cytotoxicity. II. Probable autonomy of thymus-processed lymphocytes (T-cells) for the killing of allogeneic target cells. J Exp Med 1972; 135(4):890–906.

    Article  CAS  PubMed  Google Scholar 

  5. Cantor H, Boyse EA. Functional subclasses of T-lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen. J Exp Med 1975; 141(6):1376–1389.

    Article  CAS  PubMed  Google Scholar 

  6. Kisielow P, Hirst JA, Shiku H et al. Ly antigens as markers for functionally distinct subpopulations of thymus-derived lymphocytes of the mouse. Nature 1975; 253(5488):219–220.

    Article  CAS  PubMed  Google Scholar 

  7. Shiku H, Kisielow P, Bean MA et al. Expression of T-cell differentiation antigens on effector cells in cell-mediated cytotoxicity in vitro. Evidence for functional heterogeneity related to the surface phenotype of T-cells. J Exp Med 1975; 141(1):227–241.

    Article  CAS  PubMed  Google Scholar 

  8. Taswell C, MacDonald HR, Cerottini JC. Limiting dilution analysis of alloantigen-reactive T-lymphocytes. II. Effect of cortisone and cyclophosphamide on cytolytic T-lymphocyte precursor frequencies in the thymus. Thymus 1979; 1(1–2):119–131.

    CAS  PubMed  Google Scholar 

  9. Taswell C, MacDonald HR, Cerottini JC. Clonal analysis of cytolytic T-lymphocyte specificity. I. Phenotypically distinct sets of clones as the cellular basis of cross-reactivity to alloantigens. J Exp Med 1980; 151(6):1372–1385.

    Article  CAS  PubMed  Google Scholar 

  10. Taswell C. Limiting dilution assays for the determination of immunocompetent cell frequencies. I. Data analysis. J. Immunol 1981; 126(126):1614–1619.

    CAS  PubMed  Google Scholar 

  11. Czerkinsky C, Andersson G, Ekre HP et al. Reverse ELISPOT assay for clonal analysis of cytokine production. I. Enumeration of gamma-interferon-secreting cells. J Immunol Methods 1988; 110(1):29–36.

    Article  CAS  PubMed  Google Scholar 

  12. Jung T, Schauer U, Heusser C et al. Detection of intracellular cytokines by flow cytometry. J Immunol Methods 1993; 159(1–2):197–207.

    Article  Google Scholar 

  13. Maino VC, Suni MA, Ruitenberg JJ. Rapid flow cytometric method for measuring lymphocyte subset activation. Cytometry 1995; 20(2):127–133.

    Article  CAS  PubMed  Google Scholar 

  14. Picker LJ, Singh MK, Zdraveski Z et al. Direct demonstration of cytokine synthesis heterogeneity among human memory/effector T-cells by flow cytometry. Blood 1995; 86(4):1408–1419.

    CAS  PubMed  Google Scholar 

  15. Altman JD, Moss PAH, Goulder PJR et al. Phenotypic analysis of antigen-specific T-lymphocytes. Science 1996; 274(5284):94–96.

    Article  CAS  PubMed  Google Scholar 

  16. Murali-Krishna K, Altman JD, Suresh M et al. Counting antigen-specific CD8 T-cells: A reevaluation of bystander activation during viral infection. Immunity 1998; 8:177–187.

    Article  CAS  PubMed  Google Scholar 

  17. Butz EA, Bevan MJ. Massive expansion of antigen-specific CD8+ T-cells during an acute virus infection. Immunity 1998; 8:167–175.

    Article  CAS  PubMed  Google Scholar 

  18. Harrington LE, Most Rv R, Whitton JL et al. Recombinant vaccinia virus-induced T-cell immunity: quantitation of the response to the virus vector and the foreign epitope. J Virol 2002; 76(7):3329–3337.

    Article  CAS  PubMed  Google Scholar 

  19. Masopust D, Vezys V, Marzo AL et al. Preferential localization of effector memory cells in nonlymphoid tissue. Science 2001; 291(5512):2413–2417.

    Article  CAS  PubMed  Google Scholar 

  20. Belz GT, Xie W, Doherty PC. Diversity of epitope and cytokine profiles for primary and secondary influenza a virus-specific cd8(+) t cell responses. J Immunol 2001; 166(7):4627–4633.

    CAS  PubMed  Google Scholar 

  21. Hogan RJ, Usherwood EJ, Zhong W et al. Activated antigen-specific CD8+ T-cells persist in the lungs following recovery from respiratory virus infections. J Immunol 2001; 166(3):1813–1822.

    CAS  PubMed  Google Scholar 

  22. Chang J, Braciale TJ. Respiratory syncytial virus infection suppresses lung CD8+ T-cell effector activity and peripheral CD8+ T-cell memory in the respiratory tract. Nat Med 2002; 8(1):54–60.

    Article  CAS  PubMed  Google Scholar 

  23. Johnson AJ, Njenga MK, Hansen MJ et al. Prevalent class I-restricted T-cell response to the Theiler’s virus epitope Db:VP2121-130 in the absence of endogenous CD4 help, tumor necrosis factor alpha, gamma interferon, perforin, or costimulation through CD28. J Virol 1999; 73(5):3702–3708.

    CAS  PubMed  Google Scholar 

  24. Marten NW, Stohlman SA, Zhou J et al. Kinetics of virus-specific CD8+-T-cell expansion and trafficking following central nervous system infection. J Virol 2003; 77(4):2775–2778.

    Article  CAS  PubMed  Google Scholar 

  25. Perfetto SP, Chattopadhyay PK, Roederer M. Seventeen-colour flow cytometry: unravelling the immune system. Nat Rev Immunol 2004; 4(8):648–655.

    Article  CAS  PubMed  Google Scholar 

  26. Hammarlund E, Lewis MW, Hansen SG et al. Duration of antiviral immunity after smallpox vaccination. Nature Medicine 2003; 9(9):1131–1137.

    Article  CAS  PubMed  Google Scholar 

  27. Slifka MK. Immunological memory to viral infection. Curr Opin Immunol 2004; 16(4):443–450.

    Article  CAS  PubMed  Google Scholar 

  28. Jenner E. An inquiry into the causes and effects of the variolae vaccinae. London: Sampson Low, 1798.

    Google Scholar 

  29. Jenner E. A continuation of facts and observations relative to the variolae vaccinae, or cowpox. London: Sampson Low, 1800

    Google Scholar 

  30. Crotty S, Felgner P, Davies H et al. Cutting Edge: Long-Term B-Cell Memory in Humans after Smallpox Vaccination. J Immunol 2003; 171(10):4969–4973.

    CAS  PubMed  Google Scholar 

  31. Terajima M, Cruz J, Raines G et al. Quantitation of CD8+ T-Cell responses to newly identified HLA-A*0201-restricted T-cell epitopes conserved among vaccinia and variola (smallpox) viruses. J Exp Med 2003; 197(7):927–932.

    Article  CAS  PubMed  Google Scholar 

  32. Kennedy JS, Frey SE, Yan L et al. Induction of human T-cell-mediated immune responses after primary and secondary smallpox vaccination. J Infect Dis 2004; 190(7):1286–1294.

    Article  PubMed  Google Scholar 

  33. Amara RR, Nigam P, Sharma S et al. Long-lived poxvirus immunity, robust CD4 help and better persistence of CD4 than CD8 T-cells. J Virol 2004; 78(8):3811–3816.

    Article  CAS  PubMed  Google Scholar 

  34. Treanor J, Wu H, Liang H et al. Immune responses to vaccinia and influenza elicited during primary versus recent or distant secondary smallpox vaccination of adults. Vaccine 2006; 24(47–48):6913–6923.

    Article  CAS  PubMed  Google Scholar 

  35. Miller JD, van der Most RG, Akondy RS et al. Human effector and memory CD8+ T-cell responses to smallpox and yellow fever vaccines. Immunity 2008; 28(5):710–722.

    Article  CAS  PubMed  Google Scholar 

  36. Panum PL. Beobachtungen uber das Maserncontagium. Virch Arch 1847; 1:492.

    Article  Google Scholar 

  37. van Els CA, Nanan R. T-cell responses in acute measles. Viral Immunol 2002; 15(3):435–450.

    Article  PubMed  Google Scholar 

  38. Jaye A, Magnusen AF, Sadiq AD et al. Ex vivo analysis of cytotoxic T-lymphocytes to measles antigens during infection and after vaccination in Gambian children. J Clin Invest 1998; 102(11):1969–1977.

    Article  CAS  PubMed  Google Scholar 

  39. Nanan R, Rauch A, Kampgen E et al. A novel sensitive approach for frequency analysis of measles virus-specific memory T-lymphocytes in healthy adults with a childhood history of natural measles. J Gen Virol 2000; 81(Pt 5):1313–1319.

    CAS  PubMed  Google Scholar 

  40. Ota MO, Ndhlovu Z, Oh S et al. Hemagglutinin protein is a primary target of the measles virus-specific HLA-A2-restricted CD8+ T-cell response during measles and after vaccination. J Infect Dis 2007; 195(12):1799–1807.

    Article  CAS  PubMed  Google Scholar 

  41. Naniche D, Garenne M, Rae C et al. Decrease in measles virus-specific CD4 T-cell memory in vaccinated subjects. J Infect Dis 2004; 190(8):1387–1395.

    Article  PubMed  Google Scholar 

  42. Sawyer WA. Persistence of yellow fever immunity. J Prev Med 1931; 5:413–428.

    Google Scholar 

  43. Co MD, Terajima M, Cruz J et al. Human cytotoxic T-lymphocyte responses to live attenuated 17D yellow fever vaccine: identification of HLA-B35-restricted CTL epitopes on nonstructural proteins NS1, NS2b, NS3 and the structural protein E. Virology 2002; 293(1):151–163.

    Article  CAS  PubMed  Google Scholar 

  44. Zaunders JJ, Dyer WB, Munier ML et al. CD127+CCR5+CD38+++ CD4+ Th1 effector cells are an early component of the primary immune response to vaccinia virus and precede development of interleukin-2+ memory CD4+ T-cells. J Virol 2006; 80(20):10151–10161.

    Article  CAS  PubMed  Google Scholar 

  45. Walker JM, Slifka MK. The immunostimulatory power of acute viral infection. Immunity 2008; 28(5):604–606.

    Article  CAS  PubMed  Google Scholar 

  46. Kennedy R, Poland GA. T-Cell epitope discovery for variola and vaccinia viruses. Rev Med Virol 2007; 17(2):93–113.

    Article  CAS  PubMed  Google Scholar 

  47. Jing L, Davies DH, Chong TM et al. An extremely diverse CD4 response to vaccinia virus in humans is revealed by proteome-wide T-cell profiling. J Virol 2008; 82(14):7120–7134.

    Article  CAS  PubMed  Google Scholar 

  48. Sylwester AW, Mitchell BL, Edgar JB et al. Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T-cells dominate the memory compartments of exposed subjects. J Exp Med 2005; 202(5):673–685.

    Article  CAS  PubMed  Google Scholar 

  49. Moutaftsi M, Bui HH, Peters B et al. Vaccinia virus-specific CD4+ T-cell responses target a set of antigens largely distinct from those targeted by CD8+ T-cell responses. J Immunol 2007; 178(11):6814–6820.

    CAS  PubMed  Google Scholar 

  50. Precopio ML, Betts MR, Parrino J et al. Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8(+) T-cell responses. J Exp Med 2007; 204(6):1405–1416.

    Article  CAS  PubMed  Google Scholar 

  51. Kannanganat S, Ibegbu C, Chennareddi L et al. Multiple-cytokine-producing antiviral CD4 T-cells are functionally superior to single-cytokine-producing cells. J Virol 2007; 81(16):8468–8476.

    Article  CAS  PubMed  Google Scholar 

  52. Sette A, Moutaftsi M, Moyron-Quiroz J et al. Selective CD4+ T-cell help for antibody responses to a large viral pathogen: deterministic linkage of specificities. Immunity 2008; 28(6):847–858.

    Article  CAS  PubMed  Google Scholar 

  53. Rock MT, Yoder SM, Wright PF et al. Differential Regulation of Granzyme and Perforin in Effector and Memory T-Cells following Smallpox Immunization. J Immunol 2005; 174(6):3757–3764.

    CAS  PubMed  Google Scholar 

  54. Nowacki TM, Kuerten S, Zhang W et al. Granzyme B production distinguishes recently activated CD8(+) memory cells from resting memory cells. Cell Immunol 2007; 247(1):36–48.

    Article  CAS  PubMed  Google Scholar 

  55. Jing L, Chong TM, Byrd B et al. Dominance and diversity in the primary human CD4 T-cell response to replication-competent vaccinia virus. J Immunol 2007; 178(10):6374–6386.

    CAS  PubMed  Google Scholar 

  56. Schmid DS. The human MHC-restricted cellular response to herpes simplex virus type 1 is mediated by CD4+, CD8-T-cells and is restricted to the DR region of the MHC complex. J Immunol 1988; 140(10):3610–3616.

    CAS  PubMed  Google Scholar 

  57. Bourgault I, Gomez A, Gomard E et al. A virus-specific CD4 +cell-mediated cytolytic activity revealed by CD8+ cell elimination regularly develops in uncloned human antiviral cell lines. J Immunol 1989; 142(1):252–256.

    CAS  PubMed  Google Scholar 

  58. Penna A, Fowler P, Bertoletti A et al. Hepatitis B virus (HBV)-specific cytotoxic T-cell (CTL) response in humans: characterization of HLA class II-restricted CTLs that recognize endogenously synthesized HBV envelope antigens. J Virol 1992; 66(2):1193–1198.

    CAS  PubMed  Google Scholar 

  59. Erickson AL, Walker CM. Class I major histocompatibility complex-restricted cytotoxic T-cell responses to vaccinia virus in humans. J Gen Virol 1993; 74(Pt 4):751–754.

    Article  PubMed  Google Scholar 

  60. Demkowicz WEJ, Littaua RA, Wang J et al. Human cytotoxic T-cell memory: long-lived responses to vaccinia virus. J Virol 1996; 70:2627–2631.

    CAS  PubMed  Google Scholar 

  61. Littaua RA, Takeda A, Cruz J et al. Vaccinia virus-specific human CD4+ cytotoxic T-lymphocyte clones. J Virol 1992; 66(4):2274–2280.

    CAS  PubMed  Google Scholar 

  62. Mitra-Kaushik S, Cruz J, Stern LJ et al. Human cytotoxic CD4 +T-cells recognize HLA-DR1-restricted epitopes on vaccinia virus proteins A24R and D1R conserved among poxviruses. J Immunol 2007; 179(2):1303–1312.

    CAS  PubMed  Google Scholar 

  63. Wahid R, Cannon MJ, Chow M. Virus-specific CD4 + and CD8 + cytotoxic T-cell responses and long-term T-cell memory in individuals vaccinated against polio. J Virol 2005; 79(10):5988–5995.

    Article  CAS  PubMed  Google Scholar 

  64. Green S, Kurane I, Pincus S et al. Recognition of dengue virus NS1-NS2a proteins by human CD4 + cytotoxic T-lymphocyte clones. Virology 1997; 234(2):383–386.

    Article  CAS  PubMed  Google Scholar 

  65. Arvin AM, Sharp M, Smith S et al. Equivalent recognition of a varicella-zoster virus immediate early protein (IE62) and glycoprotein I by cytotoxic T-lymphocytes of either CD4 +or CD8+ phenotype. J Immunol 1991; 146(1):257–264.

    CAS  PubMed  Google Scholar 

  66. Munz C, Bickham KL, Subklewe M et al. Human CD4(+) T-lymphocytes consistently respond to the latent Epstein-Barr virus nuclear antigen EBNA1. J Exp Med 2000; 191(10):1649–1660.

    Article  CAS  PubMed  Google Scholar 

  67. Gyulai Z, Endresz V, Burian K et al. Cytotoxic T-lymphocyte (CTL) responses to human cytomegalovirus pp65, IE1-Exon4, gB, pp150 and pp28 in healthy individuals: reevaluation of prevalence of IE1-specific CTLs. J Infect Dis 2000; 181(5):1537–1546.

    Article  CAS  PubMed  Google Scholar 

  68. Appay V, Zaunders JJ, Papagno L et al. Characterization of CD4(+) CTLs ex vivo. J Immunol 2002; 168(11):5954–5958.

    CAS  PubMed  Google Scholar 

  69. Rossi GA, Sacco O, Balbi B et al. Human ciliated bronchial epithelial cells: expression of the HLA-DR antigens and of the HLA-DR alpha gene, modulation of the HLA-DR antigens by gamma-interferon and antigen-presenting function in the mixed leukocyte reaction. Am J Respir Cell Mol Biol 1990; 3(5):431–439.

    CAS  PubMed  Google Scholar 

  70. Wang D, Levasseur-Acker GM, Jankowski R et al. HLA class II antigens and T-lymphocytes in human nasal epithelial cells. Modulation of the HLA class II gene transcripts by gamma interferon. Clin Exp Allergy 1997; 27(3):306–314.

    Article  CAS  PubMed  Google Scholar 

  71. Striz I, Mio T, Adachi Y et al. Effects of interferons alpha and gamma on cytokine production and phenotypic pattern of human bronchial epithelial cells. Int J Immunopharmacol 2000; 22(8):573–585.

    Article  CAS  PubMed  Google Scholar 

  72. Papon JF, Coste A, Gendron MC et al. HLA-DR and ICAM-1 expression and modulation in epithelial cells from nasal polyps. Laryngoscope 2002; 112(11):2067–2075.

    Article  CAS  PubMed  Google Scholar 

  73. Hegde NR, Johnson DC. Human cytomegalovirus US2 causes similar effects on both major histocompatibility complex class I and II proteins in epithelial and glial cells. J Virol 2003; 77(17):9287–9294.

    Article  CAS  PubMed  Google Scholar 

  74. Rees LE, Ayoub O, Haverson K et al. Differential major histocompatibility complex class II locus expression on human laryngeal epithelium. Clin Exp Immunol 2003; 134(3):497–502.

    Article  Google Scholar 

  75. Herzenberg LA, Parks D, Sahaf B et al. The history and future of the fluorescence activated cell sorter and flow cytometry: a view from Stanford. Clin Chem 2002; 48(10):1819–1827.

    CAS  PubMed  Google Scholar 

  76. Amanna IJ, Carlson NE, Slifka MK. Duration of humoral immunity to common viral and vaccine antigens. N Engl J Med 2007; 357(19):1903–1915.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Mark K. Slifka .

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Walker, J.M., Slifka, M.K. (2010). Longevity of T-Cell Memory following Acute Viral Infection. 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_8

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