异烟腙类衍生物TJU103体外对人T细胞增殖和细胞毒活性的影响

Effects of proliferation and cytotoxic activitation on T-cell blocked by TJU 103

目的 :探讨异烟腙类衍生物TJU 10 3体外对人T淋巴细胞增殖和细胞毒活性的影响。方法 :体外建立HLA半相合供、受者间单向混合淋巴细胞反应 (MLR)体系 ,利用MTT法检测TJU 10 3应用前后对淋巴细胞增殖和细胞毒活性的影响。结果 :不同浓度的TJU 10 3均能够不同程度地降低HLA半相合供、受者间混合淋巴细胞增殖反应 ,5 0mg/L为最佳反应浓度 ,增殖抑制率达 60 % ,且不影响供者淋巴细胞对原代白血病细胞的杀伤活性 (P >0 0 5 )。结论 :TJU 10 3能够特异性地与CD4+ T淋巴细胞结合 ,阻断CD4+ T淋巴细胞激活的抗原信号通路 ,在明显降低T淋巴细胞增殖反应的同时 ,不影响其细胞毒作用的发挥 ,有望用于临床HLA半相合移植过程移植物抗宿主病 (GVHD)和移植物抗白血病 (GVL)效应的免疫调节。

Objective To investigate the effects of TJU 103 on alloreactive T-cell proliferation and cytotoxicity in mixed lymphocyte reactions (MLR). Methods MTT assays were used respectively in MLR to detect the activity of proliferation and cytotoxicity on donor T-cell blocked by TJU 103. Results TJU 103 displayed significant inhibitory activity of proliferation in MLR at different concentrations,the optimal concentration of TJU 103 (50 mg/L) inhibited T-cell proliferation (60%),and the cytotoxicity of anti-leukemia was not influenced (P>0.05). Conclusion TJU 103 might specifically block CD4 + T-cell activation and exhibit significant inhibitory effects on alloreactive T-cell proliferation. The ability of anti-leukemia was not influenced at the concentration of 50 mg/L. TJU 103 might be used to regulate the immune response of GVHD and GVL in clinical HLA-mismatched transplantation.