Antigen-presenting cells in the female reproductive tract: influence of the estrous cycle on antigen presentation by uterine epithelial and stromal cells.

The objective of the present study was to define the afferent arm of the mucosal immune system in the female reproductive tract. When uterine cells were incubated with ovalbumin-specific T cells and ovalbumin, antigen presentation by purified luminal epithelial cells and stromal cells was measured. Analysis of uterine cells from intact rats throughout the reproductive cycle indicated that antigen presentation is controlled by the female sex hormones. Antigen presentation by epithelial cells was high at diestrus (day 3), when estradiol levels are elevated, and low at estrus and diestrus (days 1 and 2). In contrast, antigen presentation by stromal cells was low at diestrus (day 3) and high at estrus and diestrus (days 1 and 2). Estradiol given to ovariectomized rats stimulated epithelial cell and inhibited stromal cell antigen presentation compared with saline controls. To determine whether uterine cells interact with other cells to facilitate antigen presentation, thymus dendritic-like cells were incubated with uterine epithelial cells. Our findings indicated that antigen presentation is enhanced synergistically, suggesting that epithelial cells can interact with stromal antigen-presenting cells. Antibody neutralization studies indicated that both epithelial and stromal cell antigen presentation is mediated through class II, intercellular adhesion molecule-1 and lymphocyte function-associated molecules-1 alpha and -1 beta, which function as accessory molecules. These studies demonstrate that uterine epithelial and stromal cells are responsive to antigenic challenge and that sex hormones play a central role in regulating antigen presentation by uterine cells.