Cellular determinants of age-related decrements in the T-cell mitogen response of 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.
Flurkey
K
K
Institute of Gerontology, University of Michigan, Ann Arbor.
Miller
R A
RA
Harrison
D E
DE
D000375:Aging / Q000276:immunology*; D000818:Animals; D003208:Concanavalin A; D005260:Female; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D010835:Phytohemagglutinins; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D007376:Interleukin-2; D010835:Phytohemagglutinins; D003208:Concanavalin A