阻断共刺激通路诱导产生免疫无能状态  

Blockade of CD40/CD154 and B7/CD28 costimulatory pathways induces alloantigen-specific anergic state

作　　者：蔡勇[1] 周佩军[1] 张善中[1] 谭建明[1] 唐孝达[1] 

机构地区：[1]上海市第一人民医院肾移植科上海市器官移植中心,200080

出　　处：《中华器官移植杂志》2003年第5期290-293,共4页Chinese Journal of Organ Transplantation

基　　金：国家自然科学基金资助项目 ( 3990 0 137) ;上海市青年科技启明星计划资助项目 ( 0 1QB14 0 34 )

摘　　要：目的　探讨同时阻断CD4 0 /CD15 4和B7/CD2 8共刺激通路能否诱导产生免疫无能状态以及无能状态的逆转条件。方法　以C3H小鼠脾细胞为刺激细胞 ,BALB/c小鼠脾细胞为反应细胞 ,C5 7BL/ 6J小鼠脾细胞为第三方细胞 ,在体外双向混合淋巴细胞培养中加入不同浓度的抗CD15 4和抗CD80单克隆抗体 ,诱导产生无能细胞。在无能细胞中分别加入经γ射线照射后的C3H小鼠或C5 7BL/ 6J小鼠脾细胞 ,或者直接加入不同浓度重组小鼠白细胞介素 2 (rmIL 2 ) ,或者同时加入经γ射线照射后的C3H小鼠细胞和不同浓度的rmIL 2刺激 ,观察无能状态的逆转情况。结果　联合应用抗CD15 4和抗CD80单克隆抗体能显著抑制体外双向混合淋巴细胞培养反应的细胞增殖 ;第三方刺激细胞能够逆转无能细胞的无能状态 ;单纯加入rmIL 2或C3H小鼠细胞再次刺激不能逆转无能状态 ,而只有同时加入C3H小鼠细胞和rmIL 2刺激才能逆转无能细胞的无能状态。结论　同时阻断CD4 0 /CD15 4和B7/CD2 8通路能诱导产生抗原特异性的免疫无能状态 ,而且只有同时给予抗原和外源性IL 2再次刺激才能逆转这种无能状态。Objective To investigate the possibility of inducing anergy by blocking the CD40/CD154 and B7/CD28 costimulatory pathways and the reversal condition of anergic cells. Methods Splenocyte proliferation in primary mixed lymphocyte reaction (MLR) consisting of BALB/c as responder and C3H as stimulator was measured by the addition of different levels of anti-CD154 and anti-CD80 monocolonal antibody (mAb). To test the reversal condition of anergic cells induced by combined anti-CD154 and anti-CD80 mAbs blocking, C3H or C57BL/6J spleenocytes were irradiated, or different concentrations of recombinant mouse interleukin-2 (rmIL-2), or both C3H splenocytes and rmIL-2 were added to the anergic cells. Results The proliferation of anergic cells treated with both mAbs in the primary MLR was strongly inhibited in a dose-dependent manner. The cells proliferated in response to third party (C57BL/6J) stimulator. The cells did not respond to original (C3H) stimulator, and they also failed to proliferated in response to the addition of exogenous IL-2. Furthermore, the anergic state was reversed by both original (C3H) stimulator and the addition of exogenous rmIL-2. Conclusion The blockade of CD40/CD154 and B7/CD28 costimulatory pathways induces alloantigen-specific anergy, and the anergic state can be reversed by both antigen restimulation and the addition of exogenous IL-2.

关 键 词：共刺激通路 免疫无能状态 淋巴细胞 逆转条件 

分 类 号：R392[医药卫生—免疫学]