Murine T cell determination of pregnancy outcome .1. Effects of strain, alpha beta T cell receptor, gamma delta T cell receptor, and gamma delta T cell subsets

PROBLEM: T cells bearing alpha beta T cell receptor (TcR) and gamma delta TcR are present at the fetomaternal interface, and the latter, which express surface activation markers, can react with fetal trophoblast cell antigens. What is the role of these cells? METHOD: Using stress-abortion-prone DBA/2-mated CBA/J and abortion-resistant C57/B16 mice, alpha beta, gamma delta, and CD8(+/-) T cell subsets were measured in spleen and uterine decidua. The effect of immunization against abortion and administration of anti-TcR antibody in vivo was examined, Cytokine synthesis was measured by intracellular staining of Brefeldin A-treated cells. RESULTS: Abortion-prone matings showed an unexpected accumulation of gamma delta T cells beginning in the peri-implantation period and this was suppressed by immunization against abortion, The immunization deleted gamma delta T cells producing the abortogenic cytokines, TNF-alpha. and gamma-interferon, and increased production of the anti-abortive cytokines, IL-10 and transforming growth factor-beta 2 (TGF-P2). Immunization also boosted the number of alpha beta T cells which were present in the decidua as early as 2 days after implantation, In vivo injection of GL4 (anti-delta) depleted gamma delta T cells producing Th1 cytokines in the peri-implantation period, and prevented abortions, whereas H57 (anti-beta) decreased the number of alpha beta T cells and led to 100% abortions. CD8(+) T cells present in peri-implant decidua before onset of abortions were mostly alpha beta TcR+, although some were gamma delta(+). Changes in gamma delta and alpha beta T cells in pregnancy were most dramatic in uterine tissue. CONCLUSION: Although decidual gamma delta T cells after formation of a distinct placenta and fetus produce anti-abortive TGF-beta 2-like molecules and IL-10, prior events can lead to abortion. High local production of TNF-alpha and gamma-interferon develop during the peri-implantation phase because of an excessive increase in the Th1 cylokine(+) subset of gamma delta cells; these cytokines may be contributed by other tissues in decidua, and the contribution of bioactive factors by gamma delta T cells may augment the cytokine pool. In contrast, alpha beta T cells (which may be inactivated by stress chat causes abortions) may mediate the anti-abortive effect of alloimmunization, Alloimmunization involves a shift From a Th1 to a Th2 pattern in the gamma delta T cells in decidua.