Influence of sex steroids on the antigen-specific primary antibody response in vitro

The effect of 17 beta-oestradiol on an Ag-specific primary antibody response in cultures of human peripheral blood mononuclear cells (PBMC), stimulated by sheep red blood cells (SRBC) was studied. Addition of 17 beta-oestradiol (2 x 10(-9) to 100 x 10(-7) M final concentration), to PBMC from adult blood donors significantly augments the Ag-specific immune response. PBMC incubated with the anti-oestrogen agent Tamoxifen (10(-6) to 10(-8) M final concentration) prior to culture were no longer stimulated to produce an increased number of anti-SRBC antibodies as compared to control cultures. The augmentation of the immune response to SRBC in treated cultures is due to an inhibiting effect of 17 beta-oestradiol on CD8+ T suppressor (Ts) cells, since preincubation with Tamoxifen, which acts by competitive binding with CD8+ oestrogen receptors reverses such an effect. The antibody response of PBMC X-irradiated with 10 Gy before culture, (in order to decrease the suppressor activity), and then stimulated with SRBC without addition of oestrogen, was increased about 40% as compared to that of unirradiated PBMC. No further increase by addition of 17 beta-oestradiol to PBMC irradiated cultures was obtained. These findings confirm that oestrogen influences the regulatory radiosensitive CD8+ Ts cells subset. T helper (Th) cells and antigen presenting cells (APC) were not modulated by oestrogens. Our study demonstrates direct immunoregulatory effects of oestrogen on human PBMC and suggests that female sex hormones and anti-oestrogens agents may play a role in the pathogenesis and treatment of some autoimmune diseases and tumors, such as breast cancer.