Divergent telomerase and CD28 expression patterns in human CD4 and CD8 T cells following repeated encounters with the same antigenic stimulus.
Induction of telomerase, the enzyme that extends telomeres, accompanies human T lymphocyte activation. Nevertheless, high proportions of memory T cells with shortened telomeres are present in vivo during HIV infection and aging. To elucidate the long-term telomerase dynamics in human T cells, longitudinal analyses were performed on T cells subjected to repeated encounters with an allogeneic cell line in long-term culture. Whereas CD4(+) and CD8(+) T cells showed similarly dramatic increases in telomerase activity following primary stimulation, by the fourth stimulation, telomerase activity was nearly undetectable in the CD8(+) subset, but remained high in the CD4(+) subset. In addition, we document the dependence of antigen-specific telomerase inducibility on CD28 and that the decline in telomerase activity parallels the loss of CD28 expression. These findings suggest stringent telomerase regulation in human T cells, a property that may ultimately contribute to telomere shortening, finite replicative potential, and loss of control over certain pathogens.
Valenzuela
Hector F
HF
Department of Pathology & Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, 90095, USA.
Effros
Rita B
RB
D000938:Antigen-Presenting Cells / Q000276:immunology; D018106:CD28 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004790:Enzyme Induction; D006801:Humans; D007156:Immunologic Memory; D007519:Isoantigens / Q000008:administration & dosage; D007700:Kinetics; D008213:Lymphocyte Activation; D019098:Telomerase / Q000096:biosynthesis / Q000378:metabolism*
D018106:CD28 Antigens; D007519:Isoantigens; D019098:Telomerase