Differential role of lipid rafts in the functions of CD4 super(+) and CD8 super(+) human T lymphocytes with aging

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 super(+) and CD8 super(+) 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 super(+) and CD8 super(+) T cells. The defect in IL-2 production by CD4 super(+) 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 super(Lck) and LAT and their association/recruitment with the lipid raft fractions of CD4 super(+) and CD8 super(+) T cells. p56 super(Lck), LAT and Akt/PKB were weakly phosphorylated in lipid rafts of stimulated CD4 super(+) T cells of elderly as compared to young donors. Lipid rafts undergo changes in their lipid composition (ganglioside M1, cholesterol) in CD4 super(+) and CD8 super(+) T cells of elderly individuals. This study emphasizes the differential role of lipid rafts in CD4 super(+) and CD8 super(+) T-cell activation in aging and suggests that the differential localization of CD28 may explain disparities in response to stimulation in human aging.