TNF-alpha-induced apoptosis in human naïve and memory CD8+ T cells in aged humans.
Recently, human CD8+ T cells have been divided into naïve, central memory (T(CM)), and two types of effector memory cells (T(EM) and T(EMRA)), which are phenotypically identified by a set of cell surface molecules. In this investigation, we have compared the relative sensitivity of these subsets to TNF-alpha-induced apoptosis in young and aged humans. Our data show increased sensitivity of naïve and T(CM) CD8+ T cells from aged humans to TNF-alpha-induced apoptosis as compared to young subjects. Both T(EM) and T(EMRA) CD8+ T cells from young and aged subjects were relatively resistant to TNF-alpha-induced apoptosis and no significant difference was observed between young and aged subjects. Increased apoptosis of naïve and T(CM) CD8+ T cells in aged humans was associated with increased activation of caspase-8 and caspase-3 as compared to young subjects. There was no difference in the expression of TNFR-I or TNFR-II on any of the four subpopulations of CD8+ T cells between young and aged subjects. These data suggest that increased TNF-alpha-induced apoptosis of naïve and T(CM) CD8+ T cells may play a role in the deficiency of naïve and T(CM) CD8+ T cells in human aging. However, apoptosis does not appear to play a major role in increased accumulation of effector memory CD8+ T cells during human aging.
Gupta
Sudhir
S
Division of Basic and Clinical Immunology, University of California, Med. Sci I C-240, Irvine, CA 92697-4096, USA. sgupta@uci.edu
Gollapudi
Sastry
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D020169:Caspases