Inhibition of Fas‐mediated apoptotic cell death of murine T lymphocytes in a mouse model of immunosenescence in linkage to deterioration in cell membrane raft function

We previously developed a transgenic mouse line into which a rabbit protein kinase Cα (PKCα) gene fused to a human CD2 promoter/enhancer was introduced, and we found that immunosenescence was facilitated in these transgenic mice. In this study, we found that along with age‐dependent increase in the level of protein expression of PKCα and its translocation to the membrane, activated T cells became less sensitive to apoptosis‐inducing anti‐Fas antibody. The capacity of T cells to express Fas antigen on their surfaces in response to anti‐CD3 and interleukin‐2 was impaired in PKCα‐transgenic mice of relatively advanced age, although background Fas expression levels on T cells from those mice were high. We then found that out of proportion to a high level of cell surface Fas expression the density of cholera toxin B (CTx)‐binding raft elements decreased in PKCα‐transgenic mice of relatively advanced age and to a lesser extent in normal mice of advanced age. Correspondingly, the expression level of raft‐associating Lck was decreased in these mice. These findings suggest for the first time that immunosenescence of T cells involves a decrease in density of cell surface CTx‐binding raft elements, which might underlie a deterioration in T‐cell signal pathway for either cell death or cell activation.