细胞毒性淋巴细胞相关抗原4融合蛋白对大鼠肝移植急性排斥反应及CD4^＋、CD8^＋T淋巴细胞的影响

Effect of cytotoxic T lymphocytic associated antigen 4 on acute rejection and CD4^＋ , CD8 ^＋ T cells after liver allotransplantation in rats

目的观察应用细胞毒性淋巴细胞相关抗原4融合蛋白（CTLA4Ig）对大鼠肝移植术后对CD4^＋、CD8^＋T细胞的影响。方法建立大鼠肝移植急性排斥反应模型，随机分为A组：对照组，B组：实验组，CTLA4Ig80μg腹腔注射。检测B7-1和B7-2mRNA的表达，检测CD4^＋、CD8^＋T淋巴细胞浸润，确定排斥反应。结果B组2、3、7dB7—1和B7—2表达均较A组降低（B7—1：0．166±0．012比0．353±0．043；0．375±0．022比0．503±0．058；0．475±0．023比0．799±0．135；P〈0．01；B，7-2：0．170±0．022比0．341±0．040；0．357±0．031比0．475±0．041；0．512±0．103比0．829±0．124；P〈0．01）。B组2、3、7dCD4^＋、CD8^＋T淋巴细胞浸润均较A组降低（CD4^＋：12．7±3．7比21．0±4．4：15．5±3．8比28．2±5．2；18．6±4．0比35．0±7．0；P〈0．01；CD8^＋：9．3±1．5比16．9±2．9；12．1±2．2比19．9．4-5．3；17．1±3．7比29．0±5．4；P〈0．01）；B组2、3、7dRAI均较A组降低（1．3±0．2比1．9±0．3，P〈0．05；2．0±0．4比2．6±0．5，P〈0．05；2．5±0．7比4．6±1．1，P〈0．01）。B组大鼠的生存期较A组明显延长[（40．9±9．3）d比（9．2±2．1）d，P〈0．01]。结论应用CTLA41g可以诱导大鼠肝脏移植免疫耐受。

Objective To observe the effects of cytotoxic T lymphocytic associated antigen 4 （CTLA4Ig） on CD4^ ＋ and CD8^ ＋ T cells after orthotopic liver transplantation in rats （ROLT）. Methods The ROLT was established. All rats were divided into 2 groups randomly （ group A ： control group, and group B： study group）. CTLA4Ig was administrated by intraperitoneal injection at a dose of 80 μg. B7 expression was detected. CD4^＋/CD8^＋T cells were measured. RAI was identified. Results The expression of BT-1 and B7-2 mRNA was decreased significantly on the 2nd, 3rd, and 7th day in group B as compared with group A （ B7-1 ： 0. 166 ± 0. 012 vs. 0. 353 ± 0. 043 ; 0. 375 ± 0. 022 vs. 0. 503 ± 0. 058 ; 0. 475 ± 0. 023 vs. 0.799±0.135;P〈0.01; B7-2：0.170±0.022 vs. 0.341 ±0.040; 0.357 ±0.031 vs. 0.475± 0. 041 ; 0. 512 ± 0. 103 vs. 0. 829 ± 0. 124 ; P 〈 0. 01 ）. The infiltration of CD4 ±/CD8 ± T cells was decreased significantly on the 2nd, 3rd, and 7th day in group B as compared with group A （ CD4 ± 12. 7 ± 3.7 vs. 21.0±4.4; 15.5 ±3.8 vs. 28.2 ±5.2; 18.6 ±4.0 vs. 35.0±7.0;P〈0.01; CD8±： 9.3 ± 1.5 vs. 16.9±2.9; 12.1 ±2.2 vs. 19.9 ±5.3; 17.1±3.7 vs. 29.0±5.4;P〈0.01）. The RAI was decreased significantly on the 2nd, 3rd, and 7th day in group B as compared with group A （ 1.3 ±0. 2 vs. 1.9±0.3,P〈0.05; 2.0±0.4 vs. 2.6±0.5,P〈0.05; 2.5 ±0.7 vs. 4.6±1.1,P〈0.01）. Survival period was significantly longer in group B than in group A [ （40. 9 ± 9. 3 ） d vs. （ 9. 2 ± 2. 1 ） d, P 〈 0. 01 ]. Conclusion Rat liver allograft immune tolerance can be induced by CTLA4Ig.