| Allogeneic tissue transplants are usually rapidly rejected by a host in the absence of exogenous immunosuppression. Paradoxically, during pregnancy, a mother can tolerate the presence her semi-Alogeneic fetus for the duration of gestation. The mechanisms behind this phenomenon remain a fascinating biological problem. Several hypotheses have been proposed to explain fetal tolerance, each emphasizing the contribution of immunosuppressive hormones, anatomic specialization of the placenta, and various immunologic alterations during pregnancy. Overall, several overlapping or complementary mechanisms may be necessary to ensure reproductive success.; In many organs epithelial cells form the cellular barrier between self and non-self. Thus, anatomically, epithelial cells are likely to play an important role in the regulation of the immune response. Trophoblasts form the epithelial barrier between mother and child at the placenta and are specialized to separate maternal and fetal circulation, but allow selective transport of nutrients. Additionally, trophoblasts have evolved a number of immunologic adaptations that seem to promote fetal survival. One characteristic feature of trophoblasts is the near absence of conventional antigen presenting molecules (MHC class I and II) but the high expression of non-classical MHC class I molecules such as HLA-E, HLA-G, and CD1d.; Our laboratory has described a subset of regulatory CD8+ T-cells activated by the non-classical MHC class I molecule CD1d and a co-stimulatory molecule of the carcinoembryonic antigen family. Here we show evidence that trophoblasts can express the required activation molecules and stimulate a subset of CD8+ regulatory T-cells. Furthermore, we provide evidence that these cells may be present in vivo and suggest that they play a specific role in preventing anti-fetal antibody responses. Additionally, we contrast the phenotype of these trophoblast activated regulatory cells with analogous cells activated in the gut by intestinal epithelial cells. These data suggest that the activation requirements for CD8+ regulatory T-cells and their subsequent phenotype display tissue specificity.; In summary, these results confirm and extend our knowledge of the role of epithelial cells in immune regulation. Additionally, we provide evidence to support a more general role for regulatory T-cells in maintaining homeostasis at surfaces where foreign antigen must be tolerated. |
