Goulmy E, Blokland E, Persijn G, Paul L C, Wilmink J, van Rood J J
J Immunol. 1985 Nov;135(5):3082-6.
Previous studies have shown that lymphocytes from renal allografted patients with a good functioning graft display donor-specific cell-mediated lympholysis nonreactivity (CML-NR) in vitro. To define whether the HLA system influences the occurrence of the CML-NR, immunogenetic studies were carried out. Posttransplant lymphocytes derived from CML-NR patients were stimulated in vitro with lymphocytes from unrelated healthy blood donors, who were selected for the presence or absence of kidney donor-specific HLA antigens. The presentation of kidney donor-specific HLA-B (and -C) antigens on the lymphocytes of unrelated blood donors resulted in cytolytic nonresponsiveness, whereas presentation of the kidney donor-specific HLA-A locus antigens on lymphocytes of the unrelated blood donors revealed no cytolytic nonresponsiveness. The results, as displayed by posttransplant lymphocytes of renal allografted patients, demonstrate that the kidney donor HLA-B (and -C) antigens are responsible for the in vitro-observed, donor-specific CML-NR. Consequently, presentation of cells from panel members matched to the kidney donor at the HLA-B locus suppresses the response towards HLA-A locus antigens. The in vitro-observed cytolytic nonresponsiveness appeared not to be due to an absence of specific cytotoxic T lymphocytes, because the nonresponsiveness can be abrogated by addition of exogenous IL 2.
以往的研究表明，肾移植患者中移植肾功能良好者的淋巴细胞在体外表现出供体特异性细胞介导的淋巴细胞溶解无反应性（CML-NR）。为了确定HLA系统是否影响CML-NR的发生，进行了免疫遗传学研究。从CML-NR患者获得的移植后淋巴细胞，在体外被来自无关健康献血者的淋巴细胞刺激，这些献血者根据是否存在肾脏供体特异性HLA抗原进行选择。无关献血者淋巴细胞上呈现肾脏供体特异性HLA-B（和-C）抗原导致细胞溶解无反应性，而无关献血者淋巴细胞上呈现肾脏供体特异性HLA-A位点抗原则未显示细胞溶解无反应性。肾移植患者移植后淋巴细胞所显示的结果表明，肾脏供体HLA-B（和-C）抗原是体外观察到的供体特异性CML-NR的原因。因此，在HLA-B位点与肾脏供体匹配的供者细胞的呈现抑制了对HLA-A位点抗原的反应。体外观察到的细胞溶解无反应性似乎并非由于缺乏特异性细胞毒性T淋巴细胞，因为加入外源性IL-2可消除这种无反应性。
