DECIDUA-ASSOCIATED SUPPRESSOR CELLS IN ABORTION-PRONE DBA 2-MATED CBA/J MICE THAT RELEASE BIOACTIVE TRANSFORMING GROWTH-FACTOR BETA-2-RELATED IMMUNOSUPPRESSIVE MOLECULES EXPRESS A BONE-MARROW-DERIVED NATURAL SUPPRESSOR-CELL MARKER AND GAMMA-DELTA T-CELL RECEPTOR/

The decidua of allopregnant mice contains a novel population of Thy1(- ) Lyt1(-) CD4(-) CD8(-) asialoGM1(-) non-B small lymphocytic suppresso r cells that release transforming growth factor (TGF) beta 2-related s uppressor molecules. The ''null'' phenotype of this cell population is similar to some bone marrow-derived natural suppressor cell (NSC) pop ulations, and the latter may release TGF beta s. We now report that th e TGF beta 2-producing suppressor cells in the uterine decidua of DBA/ 2-mated CBA/J female mice-linked to prevention of abortions-are inacti vated effectively by 1E5/B5.1 but not by 2C1.1 rat monoclonal antibodi es to murine pregnancy-associated splenic NSC in the presence of compl ement. Immunostaining of a subpopulation of cells in decidua with 1E5/ B5.1 but not with 2C1.1 was shown by flow cytometry. Release of suppre ssor factor was also abrogated by 1E5/B5.1 + complement but not by 2C1 .1 + complement, and the suppressor factor was specifically neutralize d by anti-TGF beta 2 and not by anti-TGF beta 3. Splenic pregnancy NSC are susceptible to 2C1.1, produce TGF beta 1, and express CD3 and alp ha beta T-cell receptor (TcR) chains. Release of suppressor factor by the decidual NSC was abrogated by treatment with anti-CD3 (145 2C11) a nd 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. Sli ghtly more suppressive activity was released by implantation-site deci dua where there was no epithelium than from epithelialized inter-impla ntation-site decidua; no significant activity was released from placen tal tissue, but combining implantation-site tissue with placental tiss ue led to release of enhanced levels of immunosuppressive activity. Th ere appear to be subtypes of bone marrow-derived TcR+ NSC with differe nt phenotypes and tissue localization patterns in pregnancy. The previ ously reported dependence of decidual NSC activity on the presence of soluble signals from fetal trophoblast may be explainable by the abili ty of cells bearing TcR gamma delta to recognize and react to placenta l trophoblast cell antigen.