Murine T Cell Determination of Pregnancy Outcome: II. Distinct Th1 and Th2/3 Populations of Vγ1+δ6+ T Cells Influence Success and Failure of Pregnancy in CBA/J × DBA/2J Matings

At the fetomaternal interface, maternal effector cells come in intimate contact with fetal trophoblast cells which express paternal antigens. Failure of fetal trophoblast cells to activate maternal Th1 immune responses has been attributed in part to the absence of classical Class I and Class II major histocompatibilty complex (MHC) antigen expression and elaboration of factors which reduce TcR expression and shift any immune responses which may occur to Th2. Classical TcR αβ+ T cells have not been found to be able to respond to trophoblasts. Recently, TcR γδ+ T cells have been characterized in the low-abortion-rate pregnant C57Bl/10 mouse decidua, and the Vγ1+ subset may be able to respond to trophoblasts in a non-MHC-dependent manner. Trophoblast-recognizing T cells with Vγ1 receptors are also present in the decidua of CBA/J mice pregnant by DBA/2, an abortion-prone mating combination. To test the role of the Vγ1 subset of decidual γδ T cells in abortion-prone pregnancies, we altered this subset by injecting monoclonal anti-Vγ1.1 antibody on gestation day 5.5, 1 day after implantation. This reduced detectability of a Vγδ subset producing TNF-α and reduced the abortion rate. Anti-Vγ2, which reacts with a similar proportion of decidual γδ T cells as anti-Vγ1.1, failed to prevent abortions. Vδ6.3+ cells are prominent at the fetomaternal interface, and anti-Vδ6 antibody injected on day 5.5 prevented abortions. TGF-β2+ γδ cells first appear on day 8.5 of pregnancy; anti-Vγ1.1 antibody injection on day 8.5 depleted these cells and boosted abortions; anti-Vδ6.3 given on day 8.5 boosted abortions to the same level. These results suggest that two populations of Vγ1.1+δ6.3+ T cells may arise in the decidua: an early population that is Th1, abortogenic, and present during the time of implantation, and a Th2/3 cell subset that is present in the decidua later during pregnancy and which is pregnancy-protective.