Age-associated decline in responses of naive T cells to in vitro immunization reflects shift in glucocorticoid sensitivity

Naive 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 produ ce cell lines that respond to antigen rechallenge by proliferation and cyto kine secretion. T cells from older mice, however, do not respond under thes e conditions unless the dexamethasone concentration is raised to levels (10 (-7) M) that are inhibitory for T cells of young mice. Suitably timed expos ure to dexamethasone can also increase proliferative responses to polyclona l activation via the CD3 component of the T cell receptor, and again optima l responses are obtained from old mice only at steroid concentrations that are super-optimal for young T cells. Diminished sensitivity to glucocortico id effects may contribute to the poor responses of aged mice to novel immun ogens.