Immunological mechanisms of survival and "rejection" of the fetal allograft.

Abstract

Critical features of the trophoblast for immune protection in the mother are: 1) it is resistant to cytotoxic lymphocytes and antibodies; 2) it forms a physical barrier to immune effector cells, but not antibody, preventing them from reaching the fetus; 3) it signals the migration of suppressor and other functionally hyporesponsive lymphocytes into the uterine decidua and uterine lymphatics; 4) it promotes the production of maternal serum MLR blocking antibody with paternal antigen specificity. Some of these immunological features are lacking in women with recurrent abortions of immune etiology. Eleven women who aborted an additional time post immunization with paternal leukocytes were compared with 26 women who delivered infants at term post immunization. It was found that those who aborted: 1) shared more HLA D/DR and MT locus antigens with their spouses; 2) were more hyporesponsive in MLR to paternal antigens pre and post immunization; 3) failed to develop female serum MLR blocking factors post immunization; 4) failed to develop humoral antibodies to B cell alloantigens; and 5) had lymphocytes in the uterine decidua mantling the conceptus and in the uterine lymphatics that were reactive/cytotoxic to paternal stimulating alloantigens. These results are in sharp contrast with the immunodynamics of peripheral blood leukocytes and decidual leukocytes to paternal alloantigens in women who delivered infants at term post immunization.