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Cellular determinants of age-related decrements in the T-cell mitogen response of B6CBAF1 mice
K Flurkey1, R A Miller, D E Harrison
1Institute of Gerontology, University of Michigan, Ann Arbor.
Age-related changes in the cellular composition of the immune system that are associated with an impaired proliferative response to T-cell mitogens were identified for B6CBAF1 mice. The frequencies of precursors of Con A-induced IL-2-secreting cells (pHTL) and of Con A-induced cytotoxic cells (pCTL), determined by limiting dilution analysis, were lower for splenocytes from old mice, as were the proliferative responses to Con A and PHA, determined in conventional high cell density cultures for the same mice. The pHTL frequency correlated with the proliferative response to Con A (r2 = .94) and to PHA (r2 = .83) among old mice, but not among young; there were no correlations of pCTL frequency with proliferative responses. The reduced pHTL frequency in old mice resulted from: (a) an age-related doubling of the number of splenic B cells that diluted T cells, and (b) a 67% decline in the absolute number of Con A-reactive pHTL cells in the spleen that appeared despite the maintenance of normal numbers of total splenic CD4+ and CD8+ cells. Thus, both a decline in absolute pHTL numbers and an increase in the number of non-T cells in the spleen result in a diminished pHTL frequency that is closely linked to the impaired mitogen response observed for old B6CBAF1 mice.
Age-related changes in the cellular composition of the immune system that are associated with an impaired proliferative response to T-cell mitogens were identified for B6CBAF1 mice. The frequencies of precursors of Con A-induced IL-2-secreting cells (pHTL) and of Con A-induced cytotoxic cells (pCTL), determined by limiting dilution analysis, were lower for splenocytes from old mice, as were the proliferative responses to Con A and PHA, determined in conventional high cell density cultures for the same mice. The pHTL frequency correlated with the proliferative response to Con A (r2 = .94) and to PHA (r2 = .83) among old mice, but not among young; there were no correlations of pCTL frequency with proliferative responses. The reduced pHTL frequency in old mice resulted from: (a) an age-related doubling of the number of splenic B cells that diluted T cells, and (b) a 67% decline in the absolute number of Con A-reactive pHTL cells in the spleen that appeared despite the maintenance of normal numbers of total splenic CD4+ and CD8+ cells. Thus, both a decline in absolute pHTL numbers and an increase in the number of non-T cells in the spleen result in a diminished pHTL frequency that is closely linked to the impaired mitogen response observed for old B6CBAF1 mice.