Nature 369, 648 - 652 (23 June 1994); doi:10.1038/369648a0

Cytotoxic T-cell memory without antigen

Lisa. L. Lau, Beth D. Jamieson, T. Somasundaram & Rafi Ahmed^*

Department of Microbiology and Immunology, UCLA School of Medicine, Los Angeles, California 90024, USA
^* To whom correspondence should be addressed

MEMORY is a hallmark of the immune system and ever since its recognition there has been considerable interest in understanding how immunity is maintained^1–5. The current model is that long-term memory is dependent on persistent antigenic stimulation^6–11. We report here results that challenge this view and provide evidence that antigen is not essential for the maintenance of CD8⁺ T-cell memory. We show that memory CD8⁺ cytotoxic T lymphocytes persist indefinitely in the absence of priming antigen, retain the memory phenotype (CD44^hi), and provide protection against virus challenge. These findings suggest a re-evaluation of our current thinking on mechanisms involved in maintaining immunity and have implications towards designing effective vaccination strategies.

References

1.	Beverley, P. C. L. Curr. Topics Microbiol. Immun. 159, 111−122 (1990). | ChemPort |
2.	Ahmed, R. Semin. Immun. 4, 105−109 (1992). | ChemPort |
3.	Bradley, L. M., Croft, M. & Swain, S. L. Immun. Today 14, 197−199 (1993). | PubMed | ChemPort |
4.	Mackay, C. R. Adv. Immun. 53, 217−265 (1993). | PubMed | ChemPort |
5.	Sprent, J. Curr. Opin. Immun. 5, 433−438 (1993). | ChemPort |
6.	Celada, F. Prog. Allergy 15, 223−267 (1971). | PubMed | ChemPort |
7.	Gray, D. & Skarvall, H. Nature 336, 70−72 (1988). | Article | PubMed | ISI | ChemPort |
8.	Zinkernagel, R. M. Curr. Topics Microbiol. Immun. 159, 65−77 (1990). | ChemPort |
9.	Gray, D. & Matzinger, P. J. exp. Med. 174, 969−974 (1992).
10.	Oehen, S., Waldner, H., Kundig, M., Hengartner, H. & Zinkernagel, R. M. J. exp. Med. 176, 1273−1281 (1992). | Article | PubMed | ISI | ChemPort |
11.	Paul, W. (ed.) Fundamental Immunology 3rd edn 1211−1250 (Raven, New York, 1993).
12.	Tew, J. G., Phipps, R. P. & Mandel, T. E. Immun. Rev. 53, 175−201 (1980). | PubMed | ChemPort |
13.	Whitton, J. L., Southern, P. J. & Oldstone, M. B. A. Virology 162, 321−327 (1988). | Article | PubMed | ISI | ChemPort |
14.	Matloubian, M., Kolhekar, S. R., Somasundaram, T. & Ahmed, R. J. Virol. 67, 7340−7349 (1993). | PubMed | ISI | ChemPort |
15.	Jamieson, B. D. & Ahmed, R. J. exp. Med. 169, 1993−2005 (1989). | Article | PubMed | ISI | ChemPort |
16.	MacDonald, H. R., Budd, R. C. & Cerottini, J. C. Curr. Topics Microbiol. Immun. 159, 97−109 (1990). | ChemPort |
17.	Tabi, Z., Lynch, F., Ceredig, R., Allan, J. E. & Doherty, P. C. Cell. Immun. 113, 268−277 (1988). | Article | ChemPort |
18.	Ahmed, R., Salmi, A., Butler, L. D., Chiller, J. M. & Oldstone, M. B. A. J. exp. Med. 160, 521−540 (1984). | Article | PubMed | ISI | ChemPort |
19.	Ashton-Rickardt, P. G., Van Kaer, L., Schumacher, T. N. M., Ploegh, H. L. & Tonegawa, S. Cell 73, 1041−1049 (1993). | Article | PubMed | ChemPort |
20.	Hogquist, K. A., Gavin, M. A. & Bevan, M. J. J. exp. Med. 177, 1464−1473 (1993).
21.	Taswell, C. J. Immun. 126, 1614−1619 (1981). | PubMed | ISI | ChemPort |