T cell subset-specific susceptibility to aging.
With increasing age, the competence of the immune system to fight infections and tumors declines. Age-dependent changes have been mostly described for human CD8 T cells, raising the question of whether the response patterns for CD4 T cells are different. Gene expression arrays of memory CD4 T cells yielded a similar age-induced fingerprint as has been described for CD8 T cells. In cross-sectional studies, the phenotypic changes were not qualitatively different for CD4 and CD8 T cells, but occurred much more frequently in CD8 T cells. Homeostatic stability partially explained this lesser age sensitivity of CD4 T cells. With aging, naïve and central memory CD8 T cells were lost at the expense of phenotypically distinct CD8 effector T cells, while effector CD4 T cells did not accumulate. However, phenotypic shifts on central memory T cells were also more pronounced in CD8 T cells. This distinct stability in cell surface marker expression can be reproduced in vitro. The data show that CD8 T cells are age sensitive by at least two partially independent mechanisms: fragile homeostatic control and gene expression instability in a large set of regulatory cell surface molecules.
Czesnikiewicz-Guzik
Marta
M
Kathleen B. and Mason I. Lowance Center for Human Immunology, Emory University School of Medicine, Atlanta, GA30322, USA.
Lee
Won-Woo
WW
Cui
Dapeng
D
Hiruma
Yuko
Y
Lamar
David L
DL
Yang
Zhi-Zhang
ZZ
Ouslander
Joseph G
JG
Weyand
Cornelia M
CM
Goronzy
Jörg J
JJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014158:Transcription, Genetic