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Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756
Address all correspondence and requests for reprints to: Dr. C. R. Wira, Department of Physiology, Dartmouth Medical School, Borwell Building, 1 Medical Center Drive, Lebanon, New Hampshire 03756-0001. E-mail: . Charles.R.Wira{at}Dartmouth.edu
Estradiol is known to inhibit antigen presentation in the vagina. We report here that TGFß mediates the action of estradiol on vaginal antigen presenting cells (APC). When vaginal APC from ovariectomized rats were incubated with increasing concentrations of TGFß1 and TGFß2 in the presence of ovalbumin-specific T cells and ovalbumin, both TGFß1 and TGFß2 inhibited vaginal cell antigen presentation, whereas IL-6, IL-10, and TNF
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-TGFß antibody. In contrast, anti-TNF, anti-IL-6, and anti-IL-10 had no effect on antigen presentation. The effect of anti-TGFß was seen with vaginal APC from ovariectomized rats treated with estradiol for 1 d as well as 3 d. Finally, analysis of TGFß in the culture media of vaginal cells from saline- and estradiol-treated rats indicated that the TGFß produced is biologically active. In response to estradiol, vaginal cell production of TGFß 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 TGFß by vaginal cells.
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