Age associated decline in CD25 and CD28 expression correlate with an increased susceptibility to CD95 mediated apoptosis in T cells.
Immunosenescence is believed to contribute to increase susceptibility to infectious diseases and cancer in the elderly, and is caused mainly by changes in the T cell compartment. Longitudinal studies were undertaken to examine T cell surface receptor expression and apoptotic susceptibility using Staphylococcal enterotoxin B (SEB) activated human T cells as an in vitro model of an ageing T cell culture. An intracellular stain Carboxyfluorescein diacetate succinimidyl ester (CFSE) was used to assess the number of population divisions (PD) occurring in the ageing T cell culture. One major biomarker of aged T cells is a decrease in expression of CD28 and since this is an essential co-stimulatory molecule, its decreasing expression with age could compromise their activation and apoptotic capacity. Activation of T cells resulted in initial up-regulation of CD25, CD95 and CD28, although expression of CD25 and CD28 subsequently decreased with increasing PD. CD4 and CD8 T cells expressed similar CD25 profiles although CD28 expression was unique in each subset. CD4+ cells expressed the highest CD28 levels, and showed a gradual decline in expression with increasing PD, whereas CD8+ cells were low CD28 expressers, but did not appear to lose their expression as they aged. To determine T cell susceptibility to apoptosis via CD95/CD95-L interactions with increasing age, cells were challenged with CD95-L transfected CHO cells at various PD. Increased death was observed as they aged, which correlated with the decreased expression of activation markers CD25 and CD28.
Dennett
Nicola S
NS
Faculty of Applied Sciences, Centre for Research in Biomedicine, University of the West of England, Coldharbour Lane, Bristol BS16 1QY, UK.
Barcia
Rita N
RN
McLeod
Julie D
JD
D000328:Adult; D000375:Aging / Q000276:immunology*; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D018106:CD28 Antigens / Q000096:biosynthesis*; D015704:CD4 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016466:CHO Cells; D002478:Cells, Cultured; D016922:Cellular Senescence; D006224:Cricetinae; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D008137:Longitudinal Studies; D010799:Phycoerythrin; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013194:Staining and Labeling; D013211:Staphylococcus aureus; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
D018106:CD28 Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D005456:Fluorescent Dyes; D015375:Receptors, Interleukin-2; D019014:fas Receptor; D010799:Phycoerythrin; D016650:Fluorescein-5-isothiocyanate