Murine T cell determination of pregnancy outcome II. Distinct Th1 and Th2/3 populations of V gamma 1(+)delta 6(+) T cells influence success and failure of pregnancy in CBA/J x DBA/2J matings

At the fetomaternal interface, maternal effector cells come in intimate con tact with fetal trophoblast cells which express paternal antigens, Failure of fetal trophoblast cells to activate maternal Th1 immune responses has be en attributed in part to the absence of classical Class I and Class II majo r histocompatibilty complex (MHC) antigen expression and elaboration of fac tors which reduce TcR expression and shift any immune responses which may o ccur to Th2, Classical TcR alpha beta(+) T cells have not been found to be able to respond to trophoblasts. Recently, TcR gamma delta(+) T cells have been characterized in the low-abortion-rate pregnant C57B1/10 mouse decidua , and the V gamma 1(+) subset may be able to respond to trophoblasts in a n on-MHC-dependent manner. Trophoblast-recognizing T cells with V gamma 1 rec eptors 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 V gamma 1 subset of decidual gamma delta T cells in abortion-prone pregnancies, we altered this subset by injecting monoclonal anti-V gamma 1.1 antibody on gestation day 5.5, 1 day after implantation. This reduced detectability of a V gamma delta subset producing TNF-alpha and reduced the abortion rate. Anti-V gamm a 2, which reacts with a similar proportion of decidual gamma delta T cells as anti-V gamma 1.1, failed to prevent abortions. V delta 6.3(+) cells are prominent at the fetomaternal interface, and anti-VSG antibody injected on day 5.5 prevented abortions. TGF-beta 2(+) gamma delta cells first appear on day 8.5 of pregnancy; anti-V gamma 1.1 antibody injection on day 8.5 dep leted these cells and boosted abortions; anti-V delta 6.3 given on day 8.5 boosted abortions to the same level. These results suggest that two populat ions of V gamma 1.1(+)delta 6.3(+) T cells may arise in the decidua: an ear ly population that is Th1, abortogenic, and present during the time of impl antation, and a Th2/3 cell subset that is present in the decidua later duri ng pregnancy and which is pregnancy-protective. (C) 1999 Academic Press.