CD4小分子拮抗剂的筛选及功能测定

Screening and function test of CD4 small molecular compound inhibitors

目的筛选靶向CD4 D1功能表位的小分子化合物，并对其介导的免疫抑制功能进行初步评价。方法分别利用MqT以及^3H-TdR掺人法，检测小分子化合物对混合淋巴细胞反应（MLR）的抑制作用，筛选出具有一定剂量依赖抑制效应的小分子化合物；并进一步通过C57BL／6→BALB／c小鼠同种异体皮肤移植模型，对筛选出的小分子化合物的抗移植排斥作用进行初步评价。结果在筛选的19个小分子化合物中，J2呈现出良好的剂量依赖性地抑制T淋巴细胞增殖的作用。进一步抗小鼠皮肤移植排斥反应实验发现，J2能够有效延长皮肤植片的存活时间。结论小分子化合物J2具有良好的免疫抑制作用。

Objective To screen a panel of small molecular compounds targeted to CD4 functional epitopes, for potential antagonists of the interaction between CD4 and class Ⅱ MHC. Methods The effects of the compounds on the T lymphocyte proliferation were tested in mixed lymphocyte reaction （MLR） assays. Then, in vivo experiment was conducted to determine the possible immunosuppressive activity of the selected compounds, with a mouse model of skin allograft rejection. Results Among 19 compounds screened, J2 displayed some inhibitory activity, as observed that it could inhibit the MLR-induced T lymphocyte proliferation and prolong the median survival time of the skin allografts, as compared to placebo-treated control. Conclusion J2 is a preferable inhibitor of the CD4^＋ T cell function.