Skip to main content
SpringerLink
Log in

Principles of Memory CD8 T-Cells Generation in Relation to Protective Immunity

  • Chapter
Memory T Cells

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

Abstract

Memory T-cell responses are of vital importance in understanding the host’s immune response against pathogens and cancer cells and to begin establishing the correlation of protection against disease. In this review, we discuss our own data in the general context of current knowledge to sketch tentative working principles for the induction of protective T-cell responses by vaccination. We draw attention to quantitative and qualitative aspects of the initial contact with antigen, as well as to the kinetics of events leading to the generation of memory T cells thereafter. Our arguments are based on the current distinction of memory T cells into two lineages: effector memory T cells (TEM) and central memory T cells (TCM). Our provisional conclusion is that protective T-cell responses correlate positively with the T cells of the central memory phenotype. In proposing a set of working principles to enable protective memory T cells by vaccination we address vaccination both in the context of the immunologically-inexperienced and immunologically-experienced individual, respectively. Finally, we draw attention to the interplay between systemic and local immunity as important factors in determining the success of memory T-cell responses in protecting the individual. We believe that considerations on the immunodynamics of memory induction and maintenance, memory lineage differentiation and their relation to protection may help design strategies to control disease caused by pathogens and cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Zanetti M. Immunity and protection, the unfolding of a tale. Immunol Res 2007; 38:305–318.

    Article  CAS  PubMed  Google Scholar 

  2. Salk J, Zanetti M. Next Step in the Evolution of Vaccinology. Vol. 2. Progress in Vaccinology 1989:451–466.

    Google Scholar 

  3. Veiga-Fernandes H, Walter U, Bourgeois C et al. Response of naive and memory CD8+ T-cells to antigen stimulation in vivo. Nat Immunol 2000; 1:47–53.

    Article  CAS  PubMed  Google Scholar 

  4. Lanzavecchia A, Bernasconi N, Traggiai E et al. Understanding and making use of human memory B-cells. Immunol Rev 2006; 211:303–309.

    Article  CAS  PubMed  Google Scholar 

  5. Plotkin S, Orenstein W. Vaccines. 4th ed. Philadelphia: W.B. Saunders Co., 2004.

    Google Scholar 

  6. 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; 11:740–747.

    Article  CAS  PubMed  Google Scholar 

  7. Salk J, Salk D. Control of influenza and poliomyelitis with killed virus vaccines. Science 1977; 195:834–847.

    Article  CAS  PubMed  Google Scholar 

  8. Kilbourne E, Arden N. Inactivated influenza vaccines. In: Plotkin S, Orenstein W, eds. Vaccines. Philadelphia: W.B. Saunders Co., 1999:531–552.

    Google Scholar 

  9. Wrammert J, Smith K, Miller J et al. Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature 29 2008; 453:667–671.

    Google Scholar 

  10. Slifka MK, Antia R, Whitmire JK et al. Humoral immunity due to long-lived plasma cells. Immunity 1998; 8:363–372.

    Article  CAS  PubMed  Google Scholar 

  11. Bernasconi NL, Traggiai E, Lanzavecchia A. Maintenance of serological memory by polyclonal activation of human memory B-cells. Science 2002; 298:2199–2202.

    Article  CAS  PubMed  Google Scholar 

  12. Paul JR, Riordan JT, Melnick JL. Antibodies to three different antigenic types of poliomyelitis virus in sera from north Alaskan Eskimos. Am J Hyg 1951; 54:275–285.

    CAS  PubMed  Google Scholar 

  13. Panum PL. Beobachtungen uber das masernacontagium. Virchows Archives 1847; 1:492–503.

    Article  Google Scholar 

  14. Sawyer W. Persistence of yellow fever immunity. J Prevent Med 1930:413–428.

    Google Scholar 

  15. Crotty S, Felgner P, Davies H et al. Cutting edge: long-term B-cell memory in humans after smallpox vaccination. J Immunol 2003; 171:4969–4973.

    CAS  PubMed  Google Scholar 

  16. Burnet F. The Clonal Selection Theory of Acquired Immunity. London: Cambridge University Press, 1959.

    Google Scholar 

  17. Zinkernagel RM, Hengartner H. Regulation of the immune response by antigen. Science 2001; 293:251–253.

    Article  CAS  PubMed  Google Scholar 

  18. Unanue ER. Perspective on antigen processing and presentation. Immunol Rev 2002; 185:86–102.

    Article  CAS  PubMed  Google Scholar 

  19. Bretscher P, Cohn M. A theory of self-nonself discrimination. Science 1970; 169:1042–1049.

    Article  CAS  PubMed  Google Scholar 

  20. Janeway CA Jr, Medzhitov R. Lipoproteins take their toll on the host. Curr Biol 1999; 9:R879–882.

    Article  Google Scholar 

  21. Ulevitch RJ. Regulation of receptor-dependent activation of the innate immune response. J Infect Dis 2003; 187(Suppl 2):S351–355.

    Article  Google Scholar 

  22. Coutinho A, Poltorack A. Innate immunity: from lymphocyte mitogens to toll-like receptors and back. Curr Opin Immunol 2003; 15:599–602.

    Article  CAS  PubMed  Google Scholar 

  23. Ahmed R, Gray D. Immunological memory and protective immunity: understanding their relation. Science 1996; 272:54–60.

    Article  CAS  PubMed  Google Scholar 

  24. 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 

  25. Kaech SM, Hemby S, Kersh E et al. Molecular and functional profiling of memory CD8 T-cell differentiation. Cell 2002; 111:837–851.

    Article  CAS  PubMed  Google Scholar 

  26. Badovinac VP, Messingham KA, Jabbari A et al. Accelerated CD8+ T-cell memory and prime-boost response after dendritic-cell vaccination. Nat Med 2005; 11:748–756.

    Article  CAS  PubMed  Google Scholar 

  27. 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 

  28. Kaech SM, Ahmed R. Memory CD8+ T-cell differentiation: initial antigen encounter triggers a developmental program in naive cells. Nat Immunol 2001; 2:415–422.

    CAS  PubMed  Google Scholar 

  29. Mercado R, Vijh S, Allen SE et al. Early programming of T-cell populations responding to bacterial infection. J Immunol 2000; 165:6833–6839.

    CAS  PubMed  Google Scholar 

  30. Badovinac VP, Porter BB, Harty JT. Programmed contraction of CD8(+) T-cells after infection. Nat Immunol 2002; 3:619–626.

    Article  CAS  PubMed  Google Scholar 

  31. Zanetti M, Franchini G. T-cell memory and protective immunity by vaccination. Is more better? Trends Immunol 2006; 27:511–517.

    Article  CAS  PubMed  Google Scholar 

  32. Parish CR. Immune response to chemically modified flagellin. II. Evidence for a fundamental relationship between humoral and cell-mediated immunity. J Exp Med 1971; 134:21–47.

    Article  CAS  PubMed  Google Scholar 

  33. Hosken NA, Shibuya K, Heath AW et al. The effect of antigen dose on CD4+ T helper cell phenotype development in a T-cell receptor-alpha beta-transgenic model. J Exp Med 1995; 182:1579–1584.

    Article  CAS  PubMed  Google Scholar 

  34. Bretscher PA, Wei G, Menon JN et al. Establishment of stable, cell-mediated immunity that makes “susceptible” mice resistant to Leishmania major. Science 1992; 257:539–542.

    Article  CAS  PubMed  Google Scholar 

  35. Pope C, Kim SK, Marzo A et al. Organ-specific regulation of the CD8 T-cell response to Listeria monocytogenes infection. J Immunol 2001; 166:3402–3409.

    CAS  PubMed  Google Scholar 

  36. Bevan MJ, Fink PJ. The CD8 response on autopilot. Nat Immunol 2001; 2:381–382.

    CAS  PubMed  Google Scholar 

  37. Scheller LF, Azad AF. Maintenance of protective immunity against malaria by persistent hepatic parasites derived from irradiated sporozoites. Proc Natl Acad Sci USA 1995; 92:4066–4068.

    Article  CAS  PubMed  Google Scholar 

  38. Uzonna JE, Wei G, Yurkowski D et al. Immune elimination of Leishmania major in mice: implications for immune memory, vaccination and reactivation disease. J Immunol 2001; 167:6967–6974.

    CAS  PubMed  Google Scholar 

  39. Dudani R, Chapdelaine Y, Faassen Hv H et al. Multiple mechanisms compensate to enhance tumor-protective CD8(+) T-cell response in the long-term despite poor CD8(+) T-cell priming initially: comparison between an acute versus a chronic intracellular bacterium expressing a model antigen. J Immunol 2002; 168:5737–5745.

    CAS  PubMed  Google Scholar 

  40. Kundig TM, Bachmann MF, Ohashi PS et al. On T-cell memory: arguments for antigen dependence. Immunol Rev 1996; 150:63–90.

    Article  CAS  PubMed  Google Scholar 

  41. Tanchot C, Lemonnier FA, Perarnau B et al. Differential requirements for survival and proliferation of CD8 naive or memory T-cells. Science 1997; 276:2057–2062.

    Article  CAS  PubMed  Google Scholar 

  42. Janssen EM, Lemmens EE, Wolfe T et al. CD4+ T-cells are required for secondary expansion and memory in CD8+ T-lymphocytes. Nature 2003; 421:852–856.

    Article  CAS  PubMed  Google Scholar 

  43. Sun JC, Bevan MJ. Defective CD8 T-cell memory following acute infection without CD4 T-cell help. Science 2003; 300:339–342.

    Article  CAS  PubMed  Google Scholar 

  44. 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 

  45. Wang JC, Livingstone AM. Cutting edge: CD4+ T-cell help can be essential for primary CD8+ T-cell responses in vivo. J Immunol 2003; 171:6339–6343.

    CAS  PubMed  Google Scholar 

  46. 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 

  47. Langlade-Demoyen P, Garcia-Pons F, Castiglioni P et al. Role of T-cell help and endoplasmic reticulum targeting in protective CTL response against influenza virus. Eur J Immunol 2003; 33:720–728.

    Article  CAS  PubMed  Google Scholar 

  48. Janssen EM, Droin NM, Lemmens EE et al. CD4+ T-cell help controls CD8+ T-cell memory via TRAIL-mediated activation-induced cell death. Nature 2005; 434:88–93.

    Article  CAS  PubMed  Google Scholar 

  49. Berner V, Liu H, Zhou Q et al. IFN-gamma mediates CD4+ T-cell loss and impairs secondary antitumor responses after successful initial immunotherapy. Nat Med 2007; 13:354–360.

    Article  CAS  PubMed  Google Scholar 

  50. Bartholdy C, Kauffmann SO, Christensen JP et al. Agonistic anti-CD40 antibody profoundly suppresses the immune response to infection with lymphocytic choriomeningitis virus. J Immunol 2007; 178:1662–1670.

    CAS  PubMed  Google Scholar 

  51. Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965; 37:614–636.

    Article  CAS  PubMed  Google Scholar 

  52. Akbar AN, Beverley PC, Salmon M. Will telomere erosion lead to a loss of T-cell memory? Nat Rev Immunol 2004; 4:737–743.

    Article  CAS  PubMed  Google Scholar 

  53. Ouyang Q, Wagner WM, Zheng W et al. Dysfunctional CMV-specific CD8(+) T-cells accumulate in the elderly. Exp Gerontol 2004; 39:607–613.

    Article  CAS  PubMed  Google Scholar 

  54. Brenchley JM, Karandikar NJ, Betts MR et al. Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T-cells. Blood 2003; 101:2711–2720.

    Article  CAS  PubMed  Google Scholar 

  55. Ibegbu CC, Xu YX, Harris W et al. Expression of killer cell lectin-like receptor G1 on antigen-specific human CD8+ T-lymphocytes during active, latent and resolved infection and its relation with CD57. J Immunol 2005; 174:6088–6094.

    CAS  PubMed  Google Scholar 

  56. Papagno L, Spina CA, Marchant A et al. Immune activation and CD8+ T-cell differentiation towards senescence in HIV-1 infection. PLoS Biol 2004; 2:E20.

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  58. 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 

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

    Article  CAS  PubMed  Google Scholar 

  60. Barber DL, Wherry EJ, Ahmed R. Cutting Edge: Rapid in vivo killing by memory CD8 T-cells. J Immunol 2003; 171:27–31.

    CAS  PubMed  Google Scholar 

  61. Lanzavecchia A, Sallusto F. Dynamics of T-lymphocyte responses: intermediates, effectors and memory cells. Science 2000; 290:92–97.

    Article  CAS  PubMed  Google Scholar 

  62. Baron V, Bouneaud C, Cumano A et al. The repertoires of circulating human CD8(+) central and effector memory T-cell subsets are largely distinct. Immunity 2003; 18:193–204.

    Article  PubMed  Google Scholar 

  63. Marzo AL, Klonowski KD, Le Bon A et al. Initial T-cell frequency dictates memory CD8+ T-cell lineage commitment. Nat Immunol 2005; 6:793–799.

    Article  CAS  PubMed  Google Scholar 

  64. Obar JJ, Khanna KM, Lefrancois L. Endogenous naive CD8+ T-cell precursor frequency regulates primary and memory responses to infection. Immunity 2008; 28:859–869.

    Article  CAS  PubMed  Google Scholar 

  65. Allan W, Tabi Z, Cleary A et al. Cellular events in the lymph node and lung of mice with influenza. Consequences of depleting CD4+ T-cells. J Immunol 1990; 144:3980–3986.

    CAS  PubMed  Google Scholar 

  66. Lukacher AE, Braciale VL, Braciale TJ. In vivo effector function of influenza virus-specific cytotoxic T-lymphocyte clones is highly specific. J Exp Med 1984; 160:814–826.

    Article  CAS  PubMed  Google Scholar 

  67. Epstein SL, Lo CY, Misplon JA et al. Mechanism of protective immunity against influenza virus infection in mice without antibodies. J Immunol 1998; 160:322–327.

    CAS  PubMed  Google Scholar 

  68. Doherty PC, Christensen JP. Accessing complexity: the dynamics of virus-specific T-cell responses. Annu Rev Immunol 2000; 18:561–592.

    Article  CAS  PubMed  Google Scholar 

  69. Zanetti M, Castiglioni P, Rizzi M et al. B-lymphocytes as APC based genetic vaccines. Immunol Rev 2004; 199:264–278.

    Article  CAS  PubMed  Google Scholar 

  70. Bastin J, Rothbard J, Davey J et al. Use of synthetic peptides of influenza nucleoprotein to define epitopes recognized by class I-restricted cytotoxic T-lymphocytes. J Exp Med 1987; 165:1508–1523.

    Article  CAS  PubMed  Google Scholar 

  71. Gerloni M, Rizzi M, Castiglioni P et al. T-cell immunity using transgenic B-lymphocytes. Proc Natl Acad Sci USA 2004; 101:3892–3897.

    Article  CAS  PubMed  Google Scholar 

  72. Castiglioni P, Gerloni M, Zanetti M. Genetically programmed B-lymphocytes are highly efficient in inducing anti-virus protective immunity by central memory CD8 T-cells. Vaccine 2004; 23:699–708.

    Article  PubMed  Google Scholar 

  73. 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 

  74. Hel Z, Nacsa J, Tryniszewska E et al. Containment of simian immunodeficiency virus infection in vaccinated macaques: correlation with the magnitude of virus-specific pre and postchallenge CD4+ and CD8+ T-cell responses. J Immunol 2002; 169:4778–4787.

    PubMed  Google Scholar 

  75. Hel Z, Johnson JM, Tryniszewska E et al. A novel chimeric Rev, Tat and Nef (Retanef ) antigen as a component of an SIV/HIV vaccine Vaccine 2002; 20:3171–3186.

    Article  CAS  PubMed  Google Scholar 

  76. 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; 27:281–295.

    Article  CAS  PubMed  Google Scholar 

  77. Lee D, Graham BS, Chiu YL et al. Breakthrough infections during phase 1 and 2 prime-boost HIV-1 vaccine trials with canarypox vectors (ALVAC) and booster dose of recombinant gp120 or gp160. J Infect Dis 2004; 190:903–907.

    Article  PubMed  Google Scholar 

  78. Cohen J. HIV/AIDS. Hedged bet: an unusual AIDS vaccine trial. Science 2005; 309:1003.

    Article  CAS  PubMed  Google Scholar 

  79. Ingulli E, Funatake C, Jacovetty EL et al. Antigen presentation to CD8 T-cells after influenza A virus infection. J Immunol 2009; 182:29–33.

    CAS  PubMed  Google Scholar 

  80. Lo D, Quill H, Burkly L et al. A recessive defect in lymphocyte or granulocyte function caused by an integrated transgene. Am J Pathol 1992; 141:1237–1246.

    CAS  PubMed  Google Scholar 

  81. Wu L, D’Amico A, Winkel KD et al. RelB is essential for the development of myeloid-related CD8alphadendritic cells but not of lymphoid-related CD8alpha+ dendritic cells. Immunity 1998; 9:839–847.

    Article  CAS  PubMed  Google Scholar 

  82. Burkly L, Hession C, Ogata L et al. Expression of relB is required for the development of thymic medulla and dendritic cells. Nature 1995; 373:531–536.

    Article  CAS  PubMed  Google Scholar 

  83. Castiglioni P, Janssen EM, Prilliman KR et al. Cross-priming is under control of the relB gene. Scand J Immunol 2002; 56:219–223.

    Article  CAS  PubMed  Google Scholar 

  84. Castiglioni P, Lu C, Lo D et al. CD4 T-cell priming in dendritic cell-deficient mice. Int Immunol 2003; 15:127–136.

    Article  CAS  PubMed  Google Scholar 

  85. Zanetti M, Castiglioni P, Schoenberger S et al. The Role of relB in Regulating the Adaptive Immune Response. Ann N Y Acad Sci 2003; 987:249–257.

    Article  CAS  PubMed  Google Scholar 

  86. Castiglioni P, Hall de S, Jacovetty EL et al. Protection against Influenza A Virus by Memory CD8 T-Cells Requires Reactivation by Bone Marrow-Derived Dendritic Cells. J Immunol 2008; 180:4956–4964.

    CAS  PubMed  Google Scholar 

  87. Wang RF, Wang HY. Enhancement of antitumor immunity by prolonging antigen presentation on dendritic cells. Nat Biotechnol 2002; 20:149–154.

    Article  CAS  PubMed  Google Scholar 

  88. Wherry EJ, Blattman JN, Ahmed R. Low CD8 T-cell proliferative potential and high viral load limit the effectiveness of therapeutic vaccination. J Virol 2005; 79:8960–8968.

    Article  CAS  PubMed  Google Scholar 

  89. Williams MA, Bevan MJ. Shortening the infectious period does not alter expansion of CD8 T-cells but diminishes their capacity to differentiate into memory cells. J Immunol 2004; 173:6694–6702.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California, San Diego, La Jolla, CA, 92093-0815, USA

    Maurizio Zanetti, Paola Castiglioni & Elizabeth Ingulli

Authors
  1. Maurizio Zanetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paola Castiglioni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elizabeth Ingulli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maurizio Zanetti .

Editor information

Editors and Affiliations

  1. The Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California, San Diego, La Jolla, California, USA

    Maurizio Zanetti MD (Professor of Medicine) (Professor of Medicine)

  2. Laboratory of Cellular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA

    Stephen P. Schoenberger PhD (member in the Laboratory of Cellular Immunology) (member in the Laboratory of Cellular Immunology)

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Zanetti, M., Castiglioni, P., Ingulli, E. (2010). Principles of Memory CD8 T-Cells Generation in Relation to Protective Immunity. 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_9

Download citation

Publish with us

Policies and ethics

Search

Navigation