Journal
CELLULAR SIGNALLING
Volume 18, Issue 7, Pages 1017-1030Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2005.08.016
Keywords
T cells; CD4(+) T cells; CD8(+) T cells; lipid rafts; signal transduction; aging; cholesterol; CD28 co-receptor
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Lipid rafts are critical to the assembly of the T-cell receptor (TCR) signaling machinery. It is not known whether lipid raft properties differ in CD4+ and CD8+ T cells and whether there are age-related differences that may account in part for immune senescence. Data presented here showed that time-dependent interleukin-2 (IL-2) production was different between CD4+ and CD8+ T cells. The defect in IL-2 production by CD4+ T cells was not due to lower levels of expression of the TCR or CD28. There was a direct correlation between the activation of p56(Lck) and LAT and their association/recruitment with the lipid rail fractions of CD4+ and CD8+ T cells. p56(Lck), LAT and Akt/PKB were weakly phosphorylated in lipid rafts of stimulated CD4+ T cells of elderly as compared to young donors. Lipid rafts undergo changes in their lipid composition (ganglioside M1, cholesterol) in CD4+ and CD8+ T cells of elderly individuals. This study emphasizes the differential role of lipid rafts in CD4+ and CD8+ T-cell activation in aging and Suggests that the differential localization of CD28 may explain disparities in response to stimulation in human aging. (c) 2005 Elsevier Inc. All rights reserved.
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