Antigen-presenting cells in the female reproductive tract: Influence of estradiol on antigen presentation by vaginal cells

The objective of the present study was to define the afferent arm of the mu cosal immune system in the lower female reproductive tract. We report here that antigen presentation by vaginal cells is under hormonal control. When vaginal cells from ovariectomized rats treated with estradiol (0.01-10 mu g ) were incubated with ovalbumin-specific T cells and ovalbumin, a dose-depe ndent inhibition of antigen presentation was measured. In time course studi es, estradiol given to ovariectomized rats inhibited vaginal cell antigen p resentation within 24 h after a single injection, relative to that seen in saline controls. To determine whether changes in antigen presentation were attributable to the effect of estradiol on the number of antigen-presenting cells (APCs) in the vagina, tissues were analyzed by immunohistochemistry. Our findings indicate that estradiol inhibited antigen presentation withou t affecting the number of major histocompatibility complex class II positiv e cells and at a time when macrophage/dendritic cells/granulocytes in the v agina increase in response to estradiol treatment. Antibody neutralization studies indicated that antigen presentation by vaginal cells from ovariecto mized rats is mediated through class II and involves the expression of tran smembrane proteins B7.1 and B7.2. In other studies, vaginal APCs interact w ith thymus APCs to synergistically enhance antigen presentation under condi tions in which vaginal antigen presentation is inhibited by estradiol. Anal ysis of conditioned media indicates that enhancement of thymus antigen pres entation involves the release of a soluble factor(s) into the culture media of vaginal cells. When spleen cells were cocultured with vaginal cells fro m saline-treated rats, proliferation increased in the presence of concanava lin A and/or phytohemagglutinin and decreased with lipopolysaccharide, rela tive to spleen cells and mitogen alone. In contrast, when incubated with va ginal cells from estradiol-treated rats, spleen cell proliferation was not affected with concanavalin but was inhibited with phytohemagglutinin and li popolysaccharide. These studies demonstrate that estradiol regulates antige n presentation by vaginal cells and that vaginal cells, in turn, influence antigen presentation, as well as B and T cell proliferation.