CELLULAR IMMUNOLOGY 120,6 I-74 ( 1989) PGE2-Mediated lmmunosuppression by First Trimester Human Decidual Cells Blocks Activation of Maternal Leukocytes in the Decidua with Potential Anti-trophoblast Activity’ RANJIT S. PARHAR, SIMCHA YAGEL,AND PEEYUSH K. LALA* Department ofAnatomy, The University of WesternOntario, London, Ontario, Canada N6A 5CI Received October 18, 1988; acceptedJanuary 17, I989 We have earlier shown that first trimester human decidual cells and decidual macrophages suppress T lymphocyte alloreactivity in an MHC-unrestricted manner by secreting PGE2, which blocks the generation of IL-2 receptors (IL-2R) and production of IL-2 by lymphocytes but does not interfere with the interaction between IL-2 and IL-2R or the lytic function of CTL, once generated. The present study examined whether these events constituted a physiological, immu- noprotective mechanism in situ against the activation of maternal decidua-infiltrating leuko- cytes with potential anti-trophoblast cytocidal function. We examined (1) whether there was IL- 2R expression, IL-2 production, or anti-trophoblast killer activity in short-term (O-3 day) cul- tures of collagenase-dispersedfirst trimester human decidua inclusive of leukocytes; (2) if not, whether any of these parameters could be stimulated in these cultures by blocking PGEz synthe- sis with indomethacin, or neutralizing PGEz with anti-PGEZ antibody; (3) whether exogenously added recombinant IL-2 in the presence or absence of indomethacin stimulated IL-2R expres- sion or anti-trophoblast killer function in these cultures. IL-2R (as defined by Tat antigen) was measured in the whole cell population by a radioimmunoassay and further examined at the cellular level with radioautography. IL-2 production in culture supernatants was measured from the proliferative response(‘HTdR uptake) ofan IL-2-dependent (CTLL) cell line. Killer activity in fresh or cultured decidua-associated cells as well as PBL of normal or pregnant subjects was measured against “Cr-labeled targets inclusive of autologous cytotrophoblast cells or long-term human trophoblast cell lines, K562 and Daudi cells. Results revealed a complete absenceof IL- 2R expression, IL-2 production, or anti-trophoblast killer activity in the untreated cultures of the decidua, but all these parameters were significantly stimulated in the presenceof indometha- tin or anti-PGE, antibody. The indomethacin-stimulated killer cells had NK-like activity. Pres- ence of high dose exogenous IL-2 alone in these cultures strongly stimulated IL-2R expression and anti-trophoblast killer function, which were augmented further in the additional presence of indomethacin. The resultant killer cells had LAK cell-like activity. These findings suggest that PGEz secretion by first trimester human decidual cells blocks activation of maternal leukocytes in the decidua with potential anti-trophoblast killer function, by inhibiting IL-2 receptor genera- tion and IL-2 production in situ. 0 1989 Academic PBS, IX. INTRODUCTION Mechanisms which permit a survival of the semiallogeneic conceptus in nature have remained a major focus of investigation for a long time (l-5). It is now evident ’ Supported by grants from the Medical Research Council and the National Cancer Institute of Canada. ’ To whom correspondence should be addressed. 61 0008-8749/89 $3.00 Copyright 0 1989 by Academic Press, Inc. All rights of reproduction in any form reserved.