STUDIES ON THE IMMUNOLOGICAL BASIS OF FETAL TOLERANCE

我们的假设认为CSF-1是由蜕细胞分泌的

Our hypothesis suggests that CSF-1 secreted by decidual cells provides an "environment" during fetal development resulting in the induction of antigen-specific T suppressor (Ts) cells. Earlier studies in my laboratory demonstrated that foreign antigen administered during pregnancy not only induced antigen-specific Ts cells in the offspring, but also these Ts cells persisted for 16 weeks after delivery. Our studies also demonstrated the importance of decidual macrophages in successful pregnancies. The proposed studies will attempt to characterize decidual macrophages, and the development of Ts cells directed against both parental and foreign antigens during fetal development. Maternal immunization during the last trimester of pregnancy represents an important !means of providing protection to both the mother and infant against pathogenic virus and bacteria. The possibility of gamma interferon (gamma-IFN) treatment along with immunization during the last trimester of pregnancy to enhance the immune response of both, the mother and fetus providing enhanced protection for the neonate will be explored with regards to both parental and foreign antigens. The long persistence of antigen-specific Ts cells for 16 wks after questions regarding.the possibility of memory Ts cells. Experiments are designed to determine if the persistence of AgB-specific Ts cells induced during fetal development can be extended beyond 16 wks after delivery by immunization of various times prior to the loss of their tolerance, and efforts will determine if memory Ts cells are either or both T suppressor inducer effector. Attempts to isolate and characterize the receptors on antigen-specific Ts cells have been unsuccessful. Several recent studies suggest that Ts cells develop prior to the development of T cell receptors (TcR) associated with T helper or cytotoxic T cells suggesting that TcR on Ts cells are distinct. We propose to expand AgB-specific Ts cells from neonates by panning on anti-Tsfi antibody coated petri dishes, and fusing these cells with BW5147 T cells. AgB-specific Tsi cells cloned by limiting dilution will be further expanded by culturing in hollow fiber culture chambers to provide a significant increase in both their absolute cell numbers and the soluble factors secreted by these cell which can be used for their characterization.