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Human Reproduction, Vol. 14, No. 3, 650-655, March 1999
© 1999 European Society of Human Reproduction and Embryology

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

Koichi Ito1,4, Tadao Tanaka2,5, Norio Tsutsumi2, Fumiya Obata3 and Noboru Kashiwagi1

1 Department of Immunology, Kitasato University School of Medicine, 1–15–1 Kitasato, Sagamihara 228-8555, 2 Department of Obstetrics and Gynecology, National Okura Hospital, 2–10–1 Okura, Setagaya 157-0074 and 3 Department of Immunology, Kitasato University School of Allied Health Science, 1–15–1 Kitasato, Sagamihara 228-8555, Japan

We examined whether immunotherapy for recurrent spontaneous abortion (RSA) using paternal lymphocytes induces anti-T-cell receptor (TCR) idiotypic antibodies in RSA patients. The sera of these patients were assessed for inhibitory activity against mixed lymphocyte reactions (MLR) between maternal responder cells and paternal stimulator cells. Sera of four of the five women who maintained pregnancy successfully after immunotherapy showed significant MLR inhibition, whereas none of the five women who had unsuccessful pregnancies showed significant MLR inhibition. These sera inhibited the MLR of autologous responder T-cells, when stimulated with lymphocytes having the same 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 with 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-autologous T-cells, stimulated with paternal lymphocytes. These results indicate that anti-TCR idiotypic antibodies were induced in RSA patients by immunotherapy. These antibodies may contribute to maintaining pregnancy by negatively regulating maternal T-cells directed against HLA-DR antigens of the fetus.

Key words: anti-idiotypic antibody/HLA/immunotherapy/recurrent spontaneous abortion/TCR

4 To whom correspondence should be addressed

5 Present address: Department of Obstetrics and Gynecology, Jikei University School of Medicine, 3–25–8 Nishishinbashi, Minato-ku 105-0003, Japan


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