Gene expression characteristics of CD28null memory phenotype CD8+ T cells and its implication in T-cell aging.
Accumulation of CD28(null)CD8(+) T cells is considered as one of the hallmarks of aging in the human immune system. However, the precise changes of CD28(null)CD8(+) T cells, compared to those of the precursor CD28(+)CD8(+) memory T cells, have not been determined. In this study, we present an analysis of the global gene expression profiles of CD28(+) and CD28(null) memory phenotype CD8(+) T cells. These two CD8(+) T subsets exhibited an overall similar gene expression profile with only a few dozen genes that were differentially expressed. A wide range of functions, including co-stimulation, effector activity, signaling, and transcription, were possessed by these differentially expressed genes, reflecting significant functional changes of CD28(null) memory phenotype CD8(+) T cells from their CD28(+) counterparts. In addition, CD28(null) memory CD8(+) T cells expressed several natural killer cell receptors and high levels of granzymes, perforin, and FasL, indicating an increasing capacity for cytotoxicity during memory CD8(+) T-cell aging. Interestingly, in vitro culture of these two subsets with interleukin-15 showed that similar gene expression changes occurred in both subsets. Our analysis provides the gene expression portraits of CD28(null) memory phenotype CD8(+) T cells and alteration from their CD28(+) counterparts and suggests potential mechanisms of T-cell aging.
Fann
Monchou
M
Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Chiu
Wai Kan
WK
Wood
William H
WH
Levine
Bruce L
BL
Becker
Kevin G
KG
Weng
Nan-Ping
NP
D000818:Animals; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D016922:Cellular Senescence / Q000235:genetics*; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000378:metabolism; D010641:Phenotype; D018121:Receptors, Cytokine / Q000378:metabolism
D018106:CD28 Antigens; D016207:Cytokines; D018121:Receptors, Cytokine