Vaginal Mucosa Serves as an Inductive Site for Tolerance

Abstract

These data demonstrate that tolerance can be induced by vaginal Ag exposure. In these experiments, mice were given vaginal agarose gel suppositories containing either 5 mg OVA or saline for 6 h. Mice were given suppositories either during the estrous (estrogen dominant) or diestrous (progesterone dominant) stage of the estrous cycle. Mice were restrained during the inoculation 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 delayed-type hypersensitivity responses by measuring footpad swelling and measuring 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 mice receiving OVA-containing suppositories during estrus compared with mice receiving saline suppositories. Concomitant decreases in the Ag-specific proliferative response were also observed in lymph node lymphocytes and splenocytes. Conversely, mice inoculated during diestrus did not show a decreased response to Ag by either footpad response or in vitro proliferation. Serum Ab titers in the estrus-inoculated mice did not decrease significantly. These data demonstrate that the reproductive tract can be an inductive site for mucosally induced tolerance. However, unlike other mucosal sites such as the lung and gastrointestinal tract, reproductive tract tolerance induction is hormonally regulated.

Differential Induction of Mucosal and Systemic Antibody Responses in Women After Nasal, Rectal, or Vaginal Immunization: Influence of the Menstrual Cycle

“…The numbers of dendritic cells (DC), MHC class II ϩ cells, and the Ag-presenting capability of macrophages and DC have been found to be minimal in the uterus, but maximal in the vagina during the progesterone-associated diestrus phase that follows ovulation in these animals (10 -12). In contrast, induction of tolerance was successful in mice when Ag was vaginally administered during the estrogen-dominant ovulatory estrus phase, but not during diestrus (13). Under the influence of progesterone, the number of layers of epithelial cells lining the vagina of rodents decreases dramatically during diestrus, which would be expected to enhance uptake of lumenal Ag.…”

Seminal fluid and reproduction: much more than previously thought

“…Thus it appears that seminal factors act primarily to optimise the likelihood of successful pregnancy. This has been supported by studies showing the addition of seminal plasma or seminal factors to assisted reproductive procedures can markedly improve pregnancy success in mice, rats, hamsters, sheep and humans [2][3][4][5][6].…”

Paternal Antigen-Bearing Cells Transferred during Insemination Do Not Stimulate Anti-Paternal CD8+ T Cells: Role of Estradiol in Locally Inhibiting CD8+ T Cell Responses

“…Intravaginal (IVAG) immunization during estrus (but not diestrus) also reduced subsequent delayed-type hypersensitivity responses (36). Human CTL activity in the uterus is present during the proliferative but not the secretory phase (postovulatory period) of the menstrual cycle and is greatest in uterine tissues from postmenopausal women (37).…”