Advertisement

Homeostatic Proliferation But not The Generation of Virus Specific Memory CD8 T Cells is Impaired in the Absence of IL-15 or IL-15Rα

  • E. John Wherry
  • Todd C. Becker
  • David Boone
  • Murali-Krishna Kaja
  • Averil Ma
  • Rafi Ahmed.
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 512)

Abstract

The generation and efficient maintenance of antigen specific memory T cells is essential for long-lasting immunological protection. Antigen specific memory CD8 T cells are known to be maintained via antigen-independent homeostatic proliferation. However, signals that drive memory T cell generation and/or influence the slow turnover of memory T cells are unknown. Recently, IL-15 has received attention for its potential effect on memory CD8 T cells. In this report we examine the role of IL-15 in the generation and maintenance of virus specific memory CD8 T cells using mice deficient in either IL-15 or the IL-15 receptor a chain. Both cytokine and receptor deficient mice mount a robust CD8 T cell response to infection with lymphocytic choriomeningitis virus (LCMV) that is initially only slightly lower than in control mice. Further, virus specific memory CD8 T cells are generated in both IL-15 -/- and IL-15Ra -/- mice. However, longitudinal analysis reveals a slow attrition of LCMV specific memory CD8 T cells in the absence of IL-15 signals. Indeed, direct examination of homeostatic proliferation reveals a severe defect in the turnover of antigen specific memory CD8 T cells in the absence of IL-15. Together these results suggest that IL-15 is not essential for the generation of memory CD8 T cells, but is required for homeostatic proliferation to maintain populations of memory cells over long periods of time.

Keywords

Specific Memory Memory Phenotype Homeostatic Proliferation Lymphocytic Choriomeningitis Virus Memory Pool 
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.
    Lau, L. L., Jamieson, B. D., Somasundaram, T., and Ahmed, R. (1994) Nature 369(6482), 648-52.CrossRefPubMedGoogle Scholar
  2. 2.
    Swain, S. L., Hu, H., and Huston, G. (1999) Science 286(5443), 1381-3.CrossRefPubMedGoogle Scholar
  3. 3.
    Murali-Krishna, K., Lau, L. L., Sambhara, S., Lemonnier, F., Altman, J., and Ahmed, R. (1999) Science 286(5443), 1377-81.CrossRefPubMedGoogle Scholar
  4. 4.
    Lodolce, J. P., Boone, D. L., Chai, S., Swain, R. E., Dassopoulos, T., Trettin, S., and Ma, A. (1998) Immunity 9(5), 669-76.CrossRefPubMedGoogle Scholar
  5. 5.
    Kennedy, M. K., Glaccum, M., Brown, S. N., Butz, E. A., Viney, J. L., Embers, M., Matsuki, N., Charrier, K., Sedger, L., Willis, C. R., Brasel, K., Morrissey, P. J., Stocking, K., Schuh, J. C., Joyce, S., and Peschon, J. J. (2000)J Exp Med 191(5), 771-80.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Zhang, X., Sun, S., Hwang, I., Tough, D. F., and Sprent, J. (1998) Immunity 8(5), 591-9.CrossRefPubMedGoogle Scholar
  7. 7.
    Ku, C. C., Murakami, M., Sakamoto, A., Kappler, J., and Marrack, P. (2000) Science 288(5466), 675-8.CrossRefPubMedGoogle Scholar
  8. 8.
    Maffei, F., Schiavoni, G., Belardelli, F., and Tough, D. F. (2001)J Immunol 167(3), 1179-87.CrossRefGoogle Scholar
  9. 9.
    Biron, C. A. (2001) Immunity 14(6), 661-4.CrossRefPubMedGoogle Scholar
  10. 10.
    Umemura, M., Nishimura, H., Hirose, K., Matsuguchi, T., and Yoshikai, Y. (2001)J Immuno1 167(2), 946-56.CrossRefGoogle Scholar
  11. 11.
    Yajima, T., Nishimura, H., Ishimitsu, R., Watase, T., Busch, D. H., Pamer, E. G., Kuwano, H., and Yoshikai, Y. (2002)J Immunol 168(3), 1198-203.CrossRefPubMedGoogle Scholar
  12. 12.
    Khan, I. A., and Casciotti, L. (1999)J Immuno1 163(8), 4503-9.Google Scholar
  13. 13.
    Khan, I. A., and Kasper, L. H. (1996)J Immuno1 157(5), 2103-8.Google Scholar
  14. 14.
    Tough, D. F., Borrow, P., and Sprent, J. (1996) Science 272(5270), 1947-50.CrossRefPubMedGoogle Scholar
  15. 15.
    Fehniger, T. A., Suzuki, K., Ponnappan, A., VanDeusen, J. B., Cooper, M. A., Florea, S. M., Freud, A. G., Robinson, M. L., Durbin, J., and Caligiuri, M. A. (2001)J Exp Med 193(2), 219-31.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Ahmed, R., Salmi, A., Butler, L. D., Chiller, J. M., and Oldstone, M. B. (1984)J Exp Med 160(2), 521-40.CrossRefPubMedGoogle Scholar
  17. 17.
    Murali-Krishna, K., Altman, J. D., Suresh, M., Sourdive, D. J., Zajac, A. J., Miller, J. D., Slansky, J., and Ahmed, R. (1998) Immunity 8(2), 177-87.CrossRefPubMedGoogle Scholar
  18. 18.
    Buchmeier, M. J., and Zajac, A. J. (1999) in Persistent Viral Infections. (Ahmed R., C. I. S. Y., ed), pp. 575-605., John Wiley & Sons, Chichester, UKGoogle Scholar
  19. 19.
    Lodolce, J. P., Burkett, P. R., Boone, D. L., Chien, M., and Ma, A. (2001)J Exp Med 194(8), 1187-94.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ohteki, T., Suzue, K., Maki, C., Ota, T., and Koyasu, S. (2001) Nat Immunol 2(12), 1138-43.CrossRefPubMedGoogle Scholar
  21. 21.
    Giri, J. G., Kumaki, S., Ahdieh, M., Friend, D. J., Loomis, A., Shanebeck, K., DuBose, R., Cosman, D., Park, L. S., and Anderson, D. M. (1995) Embo J 14(15), 3654-63.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • E. John Wherry
    • 1
    • 3
  • Todd C. Becker
    • 1
    • 3
  • David Boone
    • 1
    • 3
  • Murali-Krishna Kaja
    • 1
    • 4
  • Averil Ma
    • 5
  • Rafi Ahmed.
    • 4
    • 1
    • 2
    • 3
  1. 1.These authors contributed equallyUSA
  2. 2.To whom correspondence shouldUSA
  3. 3.Emory Vaccine Center and Department of Microbiology and ImmunologyEmory University School of MedicineAtlantaUSA
  4. 4.Department of MedicineUniversity of ChicagoChicagoUSA
  5. 5.Department of ImmunologyUniversity of Washington,SeattleUSA

Personalised recommendations