Age-associated decline in responses of naïve T cells to in vitro immunization reflects shift in glucocorticoid sensitivity.
Naïve T lymphocytes from young mice can be immunized to protein antigens in vitro if the initial exposure to antigen is followed by a brief period of clonal expansion in the presence of both the glucocorticoid dexamethasone (at 10(-8) M) and antibodies to Interleukin-10 (IL-10). These cultures produce cell lines that respond to antigen rechallenge by proliferation and cytokine secretion. T cells from older mice, however, do not respond under these conditions unless the dexamethasone concentration is raised to levels (10(-7) M) that are inhibitory for T cells of young mice. Suitably timed exposure to dexamethasone can also increase proliferative responses to polyclonal activation via the CD3 component of the T cell receptor, and again optimal responses are obtained from old mice only at steroid concentrations that are super-optimal for young T cells. Diminished sensitivity to glucocorticoid effects may contribute to the poor responses of aged mice to novel immunogens.
Dozmorov
I M
IM
Department of Pathology, Geriatrics Center, University of Michigan, and Ann Arbor DVA Medical Center, 48109-0940, USA.
Miller
R A
RA
D000375:Aging / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D002999:Clone Cells / Q000187:drug effects / Q000276:immunology; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D007156:Immunologic Memory / Q000276:immunology; D016753:Interleukin-10 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D051381:Rats; D013936:Thymidine / Q000378:metabolism
D005938:Glucocorticoids; D008222:Lymphokines; D016753:Interleukin-10; D003907:Dexamethasone; D004247:DNA; D013936:Thymidine