Biochemical Society Transactions (2000) Volume 28, part 2 6 Sandell, L. L. and Zakian, V. A. (1993) Cell 75, 729–739 7 Hayflick, L. and Moorhead, P. S. (1961) Exp. Cell Res. 25, 585–621 8 Harley, C. B., Futcher, A. B. and Greider, C. W. (1990) Nature (London) 345, 458–460 9 Hastie, N. D., Dempster, M., Dunlop, M. G., Thompson, A. M., Green, D. K. and Allshire, R. C. (1990) Nature (London) 346, 866–868 10 Olovnikov, A. M. (1971) Dokl. Akad. Nauk SSSR 201, 1496–1499 11 Levy, M. Z., Allsopp, R. C., Futcher, A. B., Greider, C. W. and Harley, C. B. (1992) J. Mol. Biol. 225, 951–960 12 Wellinger, R. J., Ethier, K., Labrecque, P. and Zakian, V. A. (1996) Cell 85, 423–433 13 Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C. P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S. and Wright, W. E. (1998) Science 279, 349–352 14 de Lange, T. (1995) in Telomeres (Blackburn, E. H. C. W., ed.), pp. 265–293, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY 15 Lansdorp, P. M., Verwoerd, N. P., van de Rijke, F. M., Dragowska, V., Little, M. T., Dirks, R. W., Raap, A. K. and Tanke, H. J. (1996) Hum. Mol. Genet. 5, 685–691 16 Egholm, M., Buchardt, O. and Christensen, L. E. A. (1993) Nature (London) 365, 566–568 17 Poon, S. S. S., Martens, U. M., Ward, R. W. and Lansdorp, P. M. (1999) Cytometry 36, 267–278 18 Martens, U. M., Zijlmans, J. M., Poon, S. S., Dragowska, W., Yui, J., Chavez, E. A., Ward, R. K. and Lansdorp, P. M. (1998) Nat. Genet. 18, 76–80 19 Zijlmans, J. M., Martens, U. M., Poon, S. S., Raap, A. K., Tanke, H. J., Ward, R. K. and Lansdorp, P. M. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 7423–7428 20 Lansdorp, P. M., Poon, S., Chavez, E., Dragowska, V., Zijlmans, M., Bryan, T., Reddel, R., Egholm, M., Bacchetti, S. and Martens, U. (1997) Ciba Found. Symp. 211, 209–218 (discussion 219–222) 21 Blasco, M. A., Lee, H. W., Hande, M. P., Samper, E., Immunosenescence : potential causes and strategies for reversal R. Aspinall 1 and D. Andrew Department of Immunology, Imperial College of Medicine at Chelsea & Westminster Hospital, 369 Fulham Road, London SW10 9NH, U.K. Abstract Age-related deterioration in immune function has been recognized in many species. In humans the clinical manifestation of such immune dysfunction is age-related increases in the susceptibility to certain infections and in the incidence of some autoimmune disease and certain cancers. Lab- oratory investigations reveal age-related changes Key words : immune dysfunction, interleukin 7, T cells, thymus. Abbreviations used : IL-7, interleukin 7 ; TCR, T cell receptor ; TN, triple-negative. 1 To whom correspondence should be addressed. Lansdorp, P. M., DePinho, R. A. and Greider, C. W. (1997) Cell 91, 25–34 22 Zhu, L., Hathcock, K. S., Hande, P., Lansdorp, P. M., Seldin, M. F. and Hodes, R. H. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 8648–8653 23 Wan, T. S. K., Martens, U. M., Poon, S. S. S., Tsao, S. W., Chan, L. C. and Lansdorp, P. M. (1999) Genes Chromosomes Cancer 24, 83–86 24 Greenberg, R. A., Chin, L., Femino, A., Lee, K. -H., Gottlieb, G. J., Singer, R. H., Greider, C. W. and DePinho, R. A. (1999) Cell 97, 515–525 25 Herrera, E., Samper, E., Martin-Caballero, J., Flores, J. M., Lee, H. -W. and Blasco, M. A. (1999) EMBO J. 18, 2950–2960 26 Lee, H. W., Blasco, M. A., Gottlieb, G. J., Horner, II, J. W., Greider, C. W. and DePinho, R. A. (1998) Nature (London) 392, 569–574 27 Campisi, J. (1997) Eur. J. Cancer 33, 703–709 28 Reference deleted 29 Rufer, N., Dragowska, W., Thornbury, G., Roosnek, E. and Lansdorp, P. M. (1998) Nat. Biotechnol. 16, 743–747 30 Vaziri, H., Schachter, F., Uchida, I., Wei, L., Zhu, X., Effros, R., Cohen, D. and Harley, C. B. (1993) Am. J. Hum. Genet. 52, 661–667 31 Vaziri, H., Dragowska, W., Allsopp, R. C., Thomas, T. E., Harley, C. B. and Lansdorp, P. M. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 9857–9860 32 Frenck, Jr., R. W., Blackburn, E. H. and Shannon, K. M. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 5607–5610 33 Weng, N. P., Hathcock, K. S. and Hodes, R. J. (1998) Immunity 9, 151–157 34 Rufer, N., Bru  mmendorf, T. H., Kolvraa, S., Bischoff, C., Christensen, K., Wadsworth, L., Schulzer, M. and Lansdorp, P. M. (1999) J. Exp. Med. 190, 157–167 35 Weng, N. P., Granger, L. and Hodes, R. J. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 10827–10832 36 Herrera, E., Samper, E., Martin-Caballero, J., Flores, J. M., Lee, H. W. and Blasco, M. A. (1999) EMBO J. 18, 2950–2960 Received 6 August 1999 in the peripheral T cell pool, in the predominant phenotype, cytokine production profiles, signal- ling function and in replicative ability following stimulus with antigen, mitogens or anti-CD3 antibody. These changes in the properties of peripheral T cells are thought to be causally linked to an age-associated involution in the thymus. Our analysis reveals that thymic involution is due to a change in the thymic microenvironment linked to a reduction in the level of available interleukin 7. Treatment with interleukin 7 leads to a reversal of thymic atrophy with increased thymopoiesis. This provides the potential to reverse the immune  2000 Biochemical Society 250