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 (AM LR) as well as the phenotypic alteration of the T cell subsets. Spleni c T cells from senescence-prone (SAM-P) and resistant (SAM-R) strains of mice were incubated with autologous non-T cells, and AMLR was measu red on day 1-5. The kinetics of AMLR responses revealed a marked alter ation in senescent SAM-P but not in non-senescent SAM-R mice, in which the peak response occurred at day 1, the response decreasing thereaft er 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 t he aged SAM-R mice cultured with non-senescent syngeneic non-T cells s howed a very similar pattern to that cultured with autologous non-T ce lls. Flow cytometric analysis of T cell phenotype indicated that the p ercentage of CD4(+)CD45RB(hi) T cells correlated with the peak AMLR re sponses in both SAM-P an SAM-R mice, and that the percentage of the T cell subset with extrathymic properties was significantly higher in SA M-P mice. These findings suggest that the alteration in kinetics of AM LR is related to senescence but not to the strain of mice, and may ref lect a senescence-related dysfunction of the autoregulatory immune mec hanisms of T cells. (C) 1997 Elsevier Science Ireland Ltd.