Possible mechanisms of immunotherapy for maintaining pregnancy in recurrent spontaneous aborters: analysis of anti-idiotypic antibodies directed against autologous T-cell receptors

We examined whether immunotherapy for recurrent spontaneous abortion (RSA) using paternal lymphocytes induces anti-T-cell receptor (TCR) idiotypic ant ibodies in RSA patients. The sera of these patients were assessed for inhib itory activity against mixed lymphocyte reactions (MLR) between maternal re sponder cells and paternal stimulator cells. Sera of four of the five women who maintained pregnancy successfully after immunotherapy showed significa nt MLR inhibition, whereas none of the five women who had unsuccessful preg nancies showed significant MLR inhibition. These sera inhibited the MLR of autologous responder T-cells, when stimulated with lymphocytes having the s ame HLA-DR antigens as the patient's husband, but not when stimulated with lymphocytes having unrelated HLA-DR antigens, This MLR inhibitory activity was absorbed by autologous maternal T-lymphoblasts induced by stimulation w ith lymphocytes having the paternal HLA-DR type but not by those induced by stimulation with lymphocytes having other HLA-DR types. The maternal serum inhibited the proliferation of autologous T-cells, but not of non-autologo us T-cells, stimulated with paternal lymphocytes. These results indicate th at anti-TCR idiotypic antibodies were induced in RSA patients by immunother apy. These antibodies may contribute to maintaining pregnancy by negatively regulating maternal T-cells directed against HLA-DR antigens of the fetus.