Taken together, these data suggest

Taken together, these data suggest that the differences in CD8+ T cells activated by trophoblasts from those present in the intestine reflect differences in the CEA subfamily member (NCA in the case of trophoblasts, and CEA in the case of IECs) and the requirement for CD1d. The differences are also seen in distinct TCR gene usage, cellular phenotype, and function.A possible regulatory role for CD8+ T cells in vivo during pregnancyThe observation that particular Vβ-expressing T cells were consistently expanded in in vitro cocultures provided a means to search for these cells in vivo. Peripheral blood CD8+ T cells from pregnant women in their 16th to 29th wk of gestation were isolated and analyzed by a panel of Vβ-specific Abs. We defined expansion of a specific Vβ family if the percentage of these cells was >3 SDs above the mean of the controls. Intriguingly, 3 of 12 patients manifested significant expansions in CD8+Vβ9+ T cells consistent with our in vitro data (Table I⇓).A similar analysis was undertaken in term placenta (Table I⇑). Lymphocytes isolated from term placenta did not show a significant difference in the percentage of CD8+Vβ9 T cells as compared with the percentages found in normal peripheral blood. As mentioned above, term placentae do not express the necessary costimulatory molecule recognized by the B9 mAb (Fig. 1⇑C), and thus may not facilitate the expansion of Vβ9+CD8+ T cells.DiscussionIncreasing evidence implicates an immunological component to fetal tolerance. Several studies have demonstrated that the maternal immune system recognizes the semi-allogeneic fetus, but that it remains in a quiescent state (26, 27). The potential mechanisms underlying this phenomenon are likely to be complex and may involve several complementary or overlapping pathways to favor reproductive success.A cellular barrier comprised of placental trophoblasts separates a mother and her child. This arrangement would seem to implicate trophoblasts as a potential regulator of the immune environment at the maternal-fetal interface. Indeed, trophoblasts can influence the immune system during pregnancy through their expression of soluble and cell surface-associated immunomodulatory molecules. For example, trophoblasts secrete IDO, which limits the availability of the essential amino acid tryptophan, consequently limiting lymphocyte proliferation (28, 29). Normal human trophoblasts also lack the expression of MHC class II and the classical class I restriction elements HLA-A and HLA-B (2), but similar to IEC, express a variety of nonclassical class I molecules.