Oiwa K, Sakagami K, Orita K
Hiroshima J Med Sci. 1989 Mar;38(1):1-6.
Effects of anti-IL2 receptor antibody (anti-IL2 RAb) and cyclosporin A (CsA) on human T cell proliferation in primary mixed lymphocyte reaction (MLR) were investigated. Both agents inhibited the proliferative response induced by alloantigen in a dose dependent manner when they were added at the initiation of culture. We also analyzed the expression of activation antigen on responder cells and the kinetics of T lymphocyte subset proliferation during MLR using two-color flow cytometry. Cells expressing activation antigens, such as IL-2 receptor and HLA-DR, were found less frequently in anti-IL2 RAb-treated MLR culture (4.8%) than in CsA-treated MLR culture (16.5%) on day 6. Furthermore, proliferation of CD8+CD11- cells, considered a cytotoxic T cell subset, were inhibited significantly more in anti-IL2 RAb-treated MLR culture than in CsA-treated MLR culture. We further demonstrate that CsA inhibits preferentially IL-2 production and anti-IL2 RAb inhibits T cell proliferation by blocking an absorption of IL-2 by activated lymphocytes. These data suggest that anti-IL2 RAb selectively inhibits alloantigen-activated T cells and may prove to be of significant value as an immunosuppressive agent in clinical organ transplantation.
研究了抗白细胞介素2受体抗体(抗IL2 RAb)和环孢素A(CsA)对原发性混合淋巴细胞反应(MLR)中人类T细胞增殖的影响。当在培养开始时添加这两种药物时,它们均以剂量依赖性方式抑制同种异体抗原诱导的增殖反应。我们还使用双色流式细胞术分析了反应细胞上活化抗原的表达以及MLR期间T淋巴细胞亚群增殖的动力学。在第6天,在抗IL2 RAb处理的MLR培养物中表达活化抗原(如IL-2受体和HLA-DR)的细胞比在CsA处理的MLR培养物中(16.5%)更少见(4.8%)。此外,被认为是细胞毒性T细胞亚群的CD8 + CD11-细胞的增殖在抗IL2 RAb处理的MLR培养物中比在CsA处理的MLR培养物中受到更显著的抑制。我们进一步证明,CsA优先抑制IL-2的产生,而抗IL2 RAb通过阻断活化淋巴细胞对IL-2的摄取来抑制T细胞增殖。这些数据表明,抗IL2 RAb选择性抑制同种异体抗原激活的T细胞,并且可能被证明作为临床器官移植中的免疫抑制剂具有重要价值。