Senescence-related change in autologous mixed-lymphocyte reaction in senescence-accelerated mice

Using the senescence-accelerated mouse (SAM) strains, we examined the senescence-related changes of autologous mixed-lymphocyte reaction (AMLR) as well as the phenotypic alteration of the T cell subsets. Splenic T cells from senescence-prone (SAM-P) and resistant (SAM-R) strains of mice were incubated with autologous non-T cells, and AMLR was measured on day 1-5. The kinetics of AMLR responses revealed a marked alteration in senescent SAM-P but not in non-senescent SAM-R mice, in which the peak response occurred at day 1, the response decreasing thereafter up to day 5. Similar senescence-related change was observed in aged (24-month-old) SAM-R and BALB/c mice. Furthermore, the T cells from the aged SAM-R mice cultured with non-senescent syngeneic non-T cells showed a very similar pattern to that cultured with autologous non-T cells. Flow cytometric analysis of T cell phenotype indicated that the percentage of CD4+ CD45RBhi T cells correlated with the peak AMLR responses in both SAM-P and SAM-R mice, and that the percentage of the T cell subset with extrathymic properties was significantly higher in SAM-P mice. These findings suggest that the alteration in kinetics of AMLR is related to senescence but not to the strain of mice, and may reflect a senescence-related dysfunction of the autoregulatory immune mechanisms of T cells.