Decidua-Associated Suppressor Cells in Abortion-Prone DBA/2-Mated CBA/J Mice that Release Bioactive Transforming Growth Factor β2-related Immunosuppressive Molecules Express a Bone Marrow-Derived Natural Suppressor Cell Marker and γδ8 T-Cell Receptor1

The decidua of allopregnant mice contains a novel population of Thy1 Lyt1 CD4 CD8 asialoGM1- non-B small lymphocytic suppressor cells that release transforming growth factor (TGF) SS2-related suppressor molecules. The "null" phenotype of this cell population is similar to some bone marrow-derived natural suppressor cell (NSC) populations, and the latter may release TGF(beta)s. We now report that the TGF beta2-producing suppressor cells in the uterine decidua of DBA/2-mated CBA/J female mice-linked to prevention of abortions-are inactivated effectively by 1E5/B5.1 but not by 2C1.1 rat monoclonal antibodies to murine pregnancy-associated splenic NSC in the presence of complement. Immunostaining of a subpopulation of cells in decidua with 1E5/B5.1 but not with 2C1.1 was shown by flow cytometry. Release of suppressor factor was also abrogated by 1E5/B5.1 + complement but not by 2C1.1 + complement, and the suppressor factor was specifically neutralized by anti-TGF beta2 and not by anti-TGF beta3. Splenic pregnancy NSC are susceptible to 2C1.1, produce TGF beta1, and express CD3 and alpha beta T-cell receptor (TcR) chains. Release of suppressor factor by the decidual NSC was abrogated by treatment with anti-CD3 (145 2C11) and anti-TcR gamma delta (GL4) monoclonal antibodies + complement, but not by anti-TcR alpha beta (H57) + complement; and cells sorted using anti-TcR gamma delta (GL3) released suppressive activity in vitro. Slightly more suppressive activity was released by implantation-site decidua where there was no epithelium than from epithelialized inter-implantation-site decidua; no significant activity was released from placental tissue, but combining implantation-site tissue with placental tissue led to release of enhanced levels of immunosuppressive activity. There appear to be subtypes of bone marrow-derived TcR+ NSC with different phenotypes and tissue localization patterns in pregnancy. The previously reported dependence of decidual NSC activity on the presence of soluble signals from fetal trophoblast may be explainable by the ability of cells bearing TcR gamma delta to recognize and react to placental trophoblast cell antigen.