Vaginal mucosa serves as an inductive site for tolerance

These data demonstrate that tolerance can be induced by vaginal Ag exposure . In these experiments, mice were given vaginal agarose gel suppositories c ontaining either 5 mg OVA or saline for 6 h, Mice were given suppositories either during the estrous (estrogen dominant) or diestrous (progesterone do minant) stage of the estrous cycle. Mice were restrained during the inocula tion period to prevent orovaginal transmission of the Ag, After 1 wk, mice were immunized s.c. with OVA in CFA. After 3 wk, mice were tested for delay ed-type hypersensitivity responses by measuring footpad swelling and measur ing in vitro proliferation of lymphocytes to Ag, Using ELISA, the magnitude of the serum Ab response was also measured. In some mice, FITC conjugated to OVA was used to track the dissemination of the protein into the systemic tissues. The magnitude of footpad swelling was significantly reduced in mi ce receiving OVA-containing suppositories during estrus compared with mice receiving saline suppositories. Concomitant decreases in the Ag-specific pr oliferative response were also observed in lymph node lymphocytes and splen ocytes. Conversely, mice inoculated during diestrus did not show a decrease d response to Ag by either footpad response or in vitro proliferation, Seru m Ab titers in the estrus-inoculated mice did not decrease significantly. T hese data demonstrate that the reproductive tract can be an inductive site for mucosally induced tolerance. However, unlike other mucosal sites such a s the lung and gastrointestinal tract, reproductive tract tolerance inducti on is hormonally regulated.