First Author | Yokoyama T | Year | 2004 |
Journal | Immunology | Volume | 112 |
Issue | 1 | Pages | 64-71 |
PubMed ID | 15096185 | Mgi Jnum | J:90496 |
Mgi Id | MGI:3044017 | Doi | 10.1111/j.1365-2567.2004.01850.x |
Citation | Yokoyama T, et al. (2004) 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. Immunology 112(1):64-71 |
abstractText | We previously developed a transgenic mouse line into which a rabbit protein kinase Calpha (PKCalpha) 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 PKCalpha 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 PKCalpha-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 PKCalpha-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. |