Tju103和CTLA4-Ig诱导T淋巴细胞免疫耐受的比较

摘要

目的观察比较Tju103和CTLA4-Ig分别调节、诱导T淋巴细胞免疫耐受的作用.方法用经丝裂霉素处理的异基因正常BALB/c(H-2d)小鼠巨噬细胞做耐受诱导原,分别用Tju103和CTLA4-Ig体外训导、调节C57BL/6(H-2d)小鼠T淋巴细胞,通过增殖效应(单向混合淋巴细胞反应,MLR)和杀伤效应(MTT法),考察经训导的C57BL/6小鼠T淋巴细胞分别对BALB/c小鼠和CBA(H-2k)小鼠脾细胞以及EL9611(H-2d)红白血病细胞的增殖效应和杀伤效应的改变.结果经Yju103调节后,C57BL/6 小鼠T淋巴细胞对BALB/c和CBA小鼠脾细胞以及EL9611红白病细胞的增殖反应和杀伤效应抑制作用明显,未能诱导对已接触抗原(BALB/c小鼠)产生特异性免疫耐受.经CTLA4-Ig孵育后,C57BL/6 小鼠T淋巴细胞对这三种细胞的增殖反应和杀伤效应抑制作用明显;对已接触抗原呈现免疫耐受,而对第三种抗原(CBA小鼠)和EL9611白血病细胞保持反应性.结论在特异抗原存在下,Tju103和CTLA4-Ig均能明显抑制异基因小鼠T淋巴细胞增殖反应性和杀伤效应,但Tju103诱导非特异免疫抑制,而CTLA4-Ig诱导特异免疫耐受,更适合于诱导移植免耐受.%Objective: To observe and compare respective role of Tju103 and CTLA4-Ig on tolerance of induction of T lymphocytes. Methods: In the presence of mitomycin C-treated macrophages of normal BALB/c (H-2d) mice, C57BL/6 (H-2d) mice T cells were incubated with Tju103 or CTLA4-Ig. Then unidirectional MLR and MTT assays were employed respectively to study on the affection on the proliferative response and cytotoxic activity of the educated T cells of C57BL/6 mice to BALB/C mice spleen cells, CBA (H-2k) mice spleen cells and erythroleukemic cells EL9611. Results: In Tju103 group, the incubation significantly decreased proliferative response and cytotoxic activity of T cells of C57Bl/6 mice to BALB/c mice spleen tolerance of C57BL/6 mice T cells to the encountered antigen (BALB/c). In CTLA4-Ig group, the incubation also significantly decreased proliferative response and cytotoxicity of C57bl/6 mice T cells to the above three kinds of cells. Furthermore, it induced their specific tolerance to the encountered antigen without damage to their reactive ability to the third antigen and EL9611 cells. Conclusions: With challenge of the specific antigen,either Tju103 or CTLA4-Ig could significantly alone inhibit proliferative response and cytotoxic activity of allogeneic mice T cells. Tju103 produces nonspecific immune inhibition, whereas CTLA4-Ig does specific tolerance and seems to be a feasible approach in induction of tolerance in transplantation.