Signal transduction changes in T-cells with aging

Abstract

There are several functions of T-lymphocytes which are altered with aging. The cause is not exactly known. However the changes in T-lymphocyte activation could be caused by the altered T-cell receptor (TCR) signaling after ligation. The recently described membrane lipid rafts (MR) are critical to the assembly of the TCR, the CD28 coreceptor and the IL-2 receptor signaling machinery. The defect in IL-2 production by CD4+ T-cells with aging is not due to lower levels of expression of the TCR, CD28 or intracellular signaling molecules. However, there is a direct correlation between the activation of p56Lck and LAT at the cellular level and their association/recruitment with the lipid raft fractions of CD4+ and CD8+ T-cells. p56Lck, LAT and Akt/PKB are weakly phosphorylated in MR of stimulated CD4+ T-cells of elderly ascompared to young donors. Moreover, MR undergo changes in their lipid composition (ganglioside M1, cholesterol) with aging. There exists a differential role for lipid rafts in CD4+ and CD8+ T-cell activation with aging and consequently a differential localization of CD28 which may explain disparities in response to stimulation in human aging, mainly affecting the CD4+ T-lymphocyte population.