1936 Estradiol Regulates in Vitro Immune Responses

Higher serum immunoglobulin (Ig) levels are usually observed in females more than in males of several mammalian species, including man. Females also show a quantitatively and qualitatively enhanced capacity to produce antibodies after immunization (1-7). Moreover, during their fertile period, women have remarkably higher incidences of autoimmune diseases (8, 9). On the other hand, reports exist (10) indicating that males have stronger cell-mediated responses than females. These sexdependent differences in the mode and magnitude of immune reactivities are largely abolished by castration (11). A regulatory influence on the immune system has therefore been attributed to the main sex hormones (reviewed in 12). The cellular mechanisms involved in the sex hormone-induced immunomodulation are yet to be clarified. There are reports (13, 14) indicating that estradiol displays its immunoregulatory effect through the thymus, but the relevant cellular target sites for sex hormone activity in the immune system are not known. We studied the effect of estradiol and testosterone on human blood lymphocytes in pokeweed mitogen (PWM)l-stimulated cultures. We found that addition of physiological concentrations ofestradiol to PWM cultures enhanced the B cell differentiation without affecting the proliferative response. This effect was not obtained with testosterone. Cell fractionation studies revealed that estradiol apparently displays its effect by inhibiting the activity of a suppressor T cell population.