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Limiting dilution analysis of the allo-MHC anti-paternal cytotoxic T cell response. II: Recurrent spontaneous abortion and the effect of immunotherapy.

机译：异源MHC抗父系细胞毒性T细胞反应的极限稀释分析。二：反复自然流产和免疫治疗的效果。

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Using limiting dilution analysis (LDA) we determined anti-paternal cytotoxic T lymphocyte precursor (CTLp) frequencies in the peripheral blood of 10 women with unexplained recurrent spontaneous abortion (RSA) before and after immunization with paternal lymphocytes. The women and their partners were HLA tissue-typed and none of the women had anti-paternal cytotoxic antibodies (APCA) before immunization. All other known causes of RSA were excluded. All 10 women were found to have high frequencies of specific anti-paternal cytotoxic T cells before immunization (range 1/1030 to 1/9574). Splitwell analysis showed that these cytotoxic cells were specific to paternal MHC antigens. These frequencies rose significantly following immunization (range 1/683 to 1/4652). The cytotoxic T lymphocyte frequencies against an HLA-mismatched third party varied from woman to woman, but were not affected by the immunization. The LDA data conformed to single-hit kinetics, indicating that only cytotoxic T cells were limiting in the assay. Our data are in sharp contrast to the previously held view that women with RSA may be hyporesponsive to paternal MHC antigens. Immunizing such women with paternal leucocytes further sensitizes them. These findings cannot be reconciled with a favourable outcome in the treatment of RSA with immunotherapy. We would argue that this treatment is at best of unproven value, and may even be harmful. That these women may sometimes have successful pregnancies following immunotherapy testifies to the effectiveness of the classical MHC antigen-deficient trophoblast as an immunological barrier between mother and fetus.
机译：使用极限稀释分析（LDA），我们确定了10例因父系淋巴细胞免疫前后无法解释的反复自然流产（RSA）的女性外周血中的抗父系细胞毒性T淋巴细胞前体（CTLp）频率。这些妇女及其伴侣是HLA组织型的，在免疫前，没有一名妇女具有抗父细胞毒性抗体（APCA）。排除了所有其他已知的RSA原因。发现所有10名妇女在免疫前均具有高频率的特异性抗父系细胞毒性T细胞（范围为1/1030至1/9574）。 Splitwell分析表明，这些细胞毒性细胞对父系MHC抗原具有特异性。免疫后这些频率显着上升（范围为1/683至1/4652）。针对HLA不匹配的第三方的细胞毒性T淋巴细胞的频率因女性而异，但不受免疫影响。 LDA数据符合单发动力学，表明在试验中只有细胞毒性T细胞受到限制。我们的数据与以前认为RSA的女性可能对父亲MHC抗原反应低下的观点形成鲜明对比。用父本白细胞免疫这类妇女会使他们更加敏感。这些发现不能与免疫疗法治疗RSA的有利结果相吻合。我们认为，这种治疗充其量是未经证实的价值，甚至可能是有害的。这些妇女在接受免疫治疗后有时可能会成功怀孕，这证明了经典的MHC抗原缺陷型滋养细胞作为母婴间免疫屏障的有效性。

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