Initial TCR transgenic precursor frequency alters functional behaviour of CD8 T cells responding to acute infection

  • Thomas Wirth
  • John T. Harty
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 633)

The ability to mount antigen-specific T cell immune responses against invading pathogens is one of the key features of the adaptive immune system.8 Following infection dendritic cells present antigenic peptide–MHC complexes on their surface to naïve CD8 T cells patrolling secondary lymphoid organs.14 Interaction of these dendritic cells and antigen-specific naïve CD8 T cell precursors initiates a vigorous proliferative response resulting in multiple divisions and differentiation into an effector population. This initial expansion phase is then followed by a sharp decline in T cell numbers with 90–95% of all responding T cells succumbing to apoptotic cell death. The remaining T cells form a stable pool of memory cells capable of protecting the host against subsequent challenges with the same pathogen.3In order to study the kinetics of T cell expansion and the process of memory generation and maintenance, the identification of CD8 T cells specific for defined epitopes is of crucial...


Central Memory Precursor Frequency Input Number Effector Memory Cell Memory Subset 
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  1. 1.
    Altman, J.D., Moss, P.A., Goulder, P.J., Barouch, D.H., McHeyzer-Williams, M.G., Bell, J.I., McMichael, A.J., Davis, M.M. (1996). Phenotypic analysis of antigen-specific T lymphocytes. Science 274, 94–96CrossRefGoogle Scholar
  2. 2.
    Badovinac, V.P., Haring, J.S., Harty, J.T. (2007). Initial T cell receptor transgenic cell precursor frequency dictates critical aspects of the CD8(+) T cell response to infection. Immunity 26, 827–841CrossRefGoogle Scholar
  3. 3.
    Badovinac, V.P., Harty, J.T. (2006). Programming, demarcating, and manipulating CD8+ T-cell memory. Immunological Reviews 211, 67–80CrossRefGoogle Scholar
  4. 4.
    Baron, V., Bouneaud, C., Cumano, A., Lim, A., Arstila, T.P., Kourilsky, P., Ferradini, L., Pannetier, C. (2003). The repertoires of circulating human CD8(+) central and effector memory T cell subsets are largely distinct. Immunity 18, 193–204CrossRefGoogle Scholar
  5. 5.
    Blattman, J.N., Antia, R., Sourdive, D.J., Wang, X., Kaech, S.M., Murali-Krishna, K., Altman, J.D., Ahmed, R. (2002). Estimating the precursor frequency of naive antigen-specific CD8 T cells. Journal of Experimental Medicine 195, 657–664CrossRefGoogle Scholar
  6. 6.
    Bousso, P., Casrouge, A., Altman, J.D., Haury, M., Kanellopoulos, J., Abastado, J.P., Kourilsky, P. (1998). Individual variations in the murine T cell response to a specific peptide reflect variability in naive repertoires. Immunity 9, 169–178CrossRefGoogle Scholar
  7. 7.
    Bousso, P., Robey, E. (2003). Dynamics of CD8+ T cell priming by dendritic cells in intact lymph nodes. Nature Immunology 4, 579–585CrossRefGoogle Scholar
  8. 8.
    Butz, E.A., Bevan, M.J. (1998). Massive expansion of antigen-specific CD8+ T cells during an acute virus infection. Immunity 8, 167–175CrossRefGoogle Scholar
  9. 9.
    Casrouge, A., Beaudoing, E., Dalle, S., Pannetier, C., Kanellopoulos, J., Kourilsky, P. (2000). Size estimate of the alpha beta TCR repertoire of naive mouse splenocytes. Journal of Immunology 164, 5782–5787Google Scholar
  10. 10.
    Ford, M.L., Koehn, B.H., Wagener, M.E., Jiang, W., Gangappa, S., Pearson, T.C., Larsen, C.P. (2007). Antigen-specific precursor frequency impacts T cell proliferation, differentiation, and requirement for costimulation. Journal of Experimental Medicine 204, 299–309CrossRefGoogle Scholar
  11. 11.
    Foulds, K.E., Shen, H. (2006). Clonal competition inhibits the proliferation and differentiation of adoptively transferred TCR transgenic CD4 T cells in response to infection. Journal of Immunology 176, 3037–3043Google Scholar
  12. 12.
    Foulds, K.E., Zenewicz, L.A., Shedlock, D.J., Jiang, J., Troy, A.E., Shen, H. (2002). Cutting edge: CD4 and CD8 T cells are intrinsically different in their proliferative responses. Journal of Immunology 168, 1528–1532Google Scholar
  13. 13.
    Hataye, J., Moon, J.J., Khoruts, A., Reilly, C., Jenkins, M.K. (2006). Naive and memory CD4+ T cell survival controlled by clonal abundance. Science 312, 114–116CrossRefGoogle Scholar
  14. 14.
    Heath, W.R., Belz, G.T., Behrens, G.M., Smith, C.M., Forehan, S.P., Parish, I.A., Davey, G.M., Wilson, N.S., Carbone, F.R., Villadangos, J.A. (2004). Cross-presentation, dendritic cell subsets, and the generation of immunity to cellular antigens. Immunological Reviews 199, 9–26CrossRefGoogle Scholar
  15. 15.
    Huster, K.M., Busch, V., Schiemann, M., Linkemann, K., Kerksiek, K.M., Wagner, H., Busch, D.H. (2004). Selective expression of IL-7 receptor on memory T cells identifies early CD40L-dependent generation of distinct CD8+ memory T cell subsets. Proceedings of the National Academy of Sciences of the United States of America 101, 5610–5615CrossRefGoogle Scholar
  16. 16.
    Kaech, S.M., Ahmed, R. (2001). Memory CD8+ T cell differentiation: initial antigen encounter triggers a developmental program in naive cells. Nature Immunology 2, 415–422Google Scholar
  17. 17.
    Kaech, S.M., Tan, J.T., Wherry, E.J., Konieczny, B.T., Surh, C.D., Ahmed, R. (2003). Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nature Immunology 4, 1191–1198CrossRefGoogle Scholar
  18. 18.
    Kearney, E.R., Pape, K.A., Loh, D.Y., Jenkins, M.K. (1994). Visualization of peptide-specific T cell immunity and peripheral tolerance induction in vivo. Immunity 1, 327–339CrossRefGoogle Scholar
  19. 19.
    Kedzierska, K., Day, E.B., Pi, J., Heard, S.B., Doherty, P.C., Turner, S.J., Perlman, S. (2006). Quantification of repertoire diversity of influenza-specific epitopes with predominant public or private TCR usage. Journal of Immunology 177, 6705–6712Google Scholar
  20. 20.
    Kemp, R.A., Powell, T.J., Dwyer, D.W., Dutton, R.W. (2004). Cutting edge: regulation of CD8+ T cell effector population size. Journal of Immunology 173, 2923–2927Google Scholar
  21. 21.
    Lanzavecchia, A., Sallusto, F. (2000). Dynamics of T lymphocyte responses: intermediates, effectors, and memory cells. Science 290, 92–97CrossRefGoogle Scholar
  22. 22.
    Marzo, A.L., Klonowski, K.D., Le Bon, A., Borrow, P., Tough, D.F., Lefrancois, L. (2005). Initial T cell frequency dictates memory CD8+ T cell lineage commitment. Nature Immunology 6, 793–799CrossRefGoogle Scholar
  23. 23.
    Masopust, D., Vezys, V., Marzo, A.L., Lefrancois, L. (2001). Preferential localization of effector memory cells in nonlymphoid tissue. Science 291, 2413–2417CrossRefGoogle Scholar
  24. 24.
    Mempel, T.R., Henrickson, S.E., Andrian, U.H. Von (2004). T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 427, 154–159CrossRefGoogle Scholar
  25. 25.
    Moon, J.J., Chu, H.H., Pepper, M., McSorley, S.J., Jameson, S.C., Kedl, R.M., Jenkins, M.K. (2007). Naive CD4(+) T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude. Immunity 27, 203–213CrossRefGoogle Scholar
  26. 26.
    Pewe, L.L., Netland, J.M., Heard, S.B., Perlman, S. (2004). Very diverse CD8 T cell clonotypic responses after virus infections. Journal of Immunology 172, 3151–3156Google Scholar
  27. 27.
    Reiner, S.L., Sallusto, F., Lanzavecchia, A. (2007). Division of labor with a workforce of one: challenges in specifying effector and memory T cell fate. Science 317, 622–625CrossRefGoogle Scholar
  28. 28.
    Sallusto, F., Lenig, D., Forster, R., Lipp, M., Lanzavecchia, A. (1999). Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401, 708–712CrossRefGoogle Scholar
  29. 29.
    Stoll, S., Delon, J., Brotz, T.M., Germain, R.N. (2002). Dynamic imaging of T cell–dendritic cell interactions in lymph nodes. Science 296, 1873–1876CrossRefGoogle Scholar
  30. 30.
    Wherry, E.J., Teichgraber, V., Becker, T.C., Masopust, D., Kaech, S.M., Antia, R., Andrian, U.H., von Ahmed, R. (2003). Lineage relationship and protective immunity of memory CD8 T cell subsets. Nature Immunology 4, 225–234CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Thomas Wirth
    • 1
  • John T. Harty
  1. 1.Department of Microbiology, Interdisciplinary Graduate Program in ImmunologyUniversity of IowaIowa CityUSA

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