DESCRIPTION: (Investigator's Abstract) The overall goal of this application is to identify the mechanisms by which immunosuppression occurs in the mother during pregnancy, in fetus and neonate. A. Specific Aims 1. Extend ongoing studies of the factor(s) in murine amniotic fluid (MAF) which mediates in the in vitro and in vivo suppression of the immune response. a) isolate and characterize the TGF-Beta2-like immunosuppressor in MAF, determine its sequence and structural relation to other members of the TGF-Beta family; b) identify the ontogeny and sites of synthesis of membranes of the TGF-Beta family in fetal and maternal tissues by in situ hybridization and Northern analyses.2. Evaluate the role of MAF and the purified TGF-Beta2 like suppressive factor in the immune deficiencies of the fetus, neonate, pregnant, and lymphoid irradiated animal: a) evaluate the role of the MAF suppressive factor in generation and activity of suppressor cells; b) determine if the cytokines present in MAF (TGF-Beta, CSF-1) produced by the fetus and/or pregnant uterus, modulate MHC antigens and influence persistence of the fetal allograft. 3. Delineate the molecular mechanisms of immunosuppression by MAF and its cytokine components using normal macrophages, and macrophage and B-cell lines. a) examine modulation of cell surface Ia and Ia gene expression by MAF, CSF-1 and TGF-Beta and their interactions with other cytokines known to induce Ia expression (GM-CSF, IL-4, IFN-gamma); b) study the molecular mechanisms (transcriptional regulation, DNA binding proteins and 5' sequences) involved in the response of macrophages to cytokines that positively (IFN-gamma, GM-CSF, IL-4) or negatively (CSF-1, TGF-Beta) regulate Ia gene expression. 4. To evaluate MAF, TGF-Beta and CSF-1 as immunosuppressive agents capable of inhibiting rodent transplant rejection (cardiac and renal) and murine GVH disease.