Estradiol-induced alteration in the immune system. II. Suppression of cellular immunity in the rat is not the result of direct estrogenic action.

Estradiol has been reported to suppress numerous cellular immune response. What is not known is how estradiol exerts this effect. In vivo administration of estradiol to male rats caused time-related immunomodulatory effects leading to enhancement of lymphocyte transformation while suppressing a mixed lymphocyte reaction (MLR) response. The suppression of the MLR response was not due to alterations in the ratio of helper and suppressor T cells, nor was it due to alterations in either cell viability or the number of cells in culture. Lymphocytes cultured in vitro with estradiol, however, fail to show any alteration in the responsiveness in either MLR or lymphocyte transformation assays. The suppressive effects of estradiol cannot be transferred from a primary MLR culture to a second MLR culture using the supernatants from the primary MLR culture. Lymphocytes from animals given estradiol in vivo show no alteration in the production of interleukin 2: added in vitro to primary MLR cultures, Interleukin 2 failed to restore full responsiveness to lymphocytes from animals treated in vivo with estradiol. These results suggest that estradiol acts indirectly to cause an alteration in the responsiveness of the regulatory cells of the cellular immune system.