Antigen Presentation by Vaginal Cells: Role of TGFβ as a Mediator of Estradiol Inhibition of Antigen Presentation

Abstract

Estradiol is known to inhibit antigen presentation in the vagina. We report here that TGFβ mediates the action of estradiol on vaginal antigen presenting cells (APC). When vaginal APC from ovariectomized rats were incubated with increasing concentrations of TGFβ1 and TGFβ2 in the presence of ovalbumin-specific T cells and ovalbumin, both TGFβ1 and TGFβ2 inhibited vaginal cell antigen presentation, whereas IL-6, IL-10, and TNFα had no consistent effect. In other experiments, estradiol-induced inhibition of antigen presentation by vaginal cells was partially reversed when vaginal APC were incubated with anti-TGFβ antibody. In contrast, anti-TNFα, anti-IL-6, and anti-IL-10 had no effect on antigen presentation. The effect of anti-TGFβ was seen with vaginal APC from ovariectomized rats treated with estradiol for 1 d as well as 3 d. Finally, analysis of TGFβ in the culture media of vaginal cells from saline- and estradiol-treated rats indicated that the TGFβ produced is biologically active. In response to estradiol, vaginal cell production of TGFβ was significantly greater than that seen with control cells. These studies suggest that estradiol regulation of antigen presentation by vaginal cells is mediated through the local production of TGFβ by vaginal cells.