Costimulatory mechanisms in the elderly.
Aging is associated with the progressive increase of T cells that lack expression of the CD28 costimulatory molecule. Because CD28/B7 signal transduction is required for proliferation, T cells lacking CD28 gene expression are incapable of clonal expansion. To determine whether CD28- T cells are a separate lineage or, alternatively, are the progeny of formerly CD28+ T cells, we performed cell culture longitudinal analysis on the same population of T cells over time. Repeated antigen-induced T cell division ultimately leads to irreversible cell cycle arrest, shortened telomeres, loss of telomerase inducibility, and total absence of expression of CD28. This in vitro model has elucidated a novel facet of T cell biology that may explain the increased incidence of infection and cancer in the elderly.
Effros
R B
RB
Department of Pathology and Laboratory Medicine, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095-1732, USA. reffros@mednet.ucla.edu
D000375:Aging / Q000276:immunology*; D018106:CD28 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D002455:Cell Division; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008954:Models, Biological; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D019098:Telomerase / Q000378:metabolism
D018106:CD28 Antigens; D019098:Telomerase