T细胞疫苗诱导同种抗原特异性免疫耐受的实验研究

目的　探讨T细胞疫苗诱导同种异体免疫耐受的作用及其机制。方法　制备BN大鼠针对Lou/C大鼠 (同种异体抗原 )的T细胞疫苗 (LCTCV)及针对Lewis大鼠 (同种无关抗原 )的T细胞疫苗 (LTCV) ,然后分别免疫正常BN大鼠 ,连续 3周 ,每周 1次 ,同时设空白对照。以被免疫BN大鼠的脾细胞作为反应细胞 ,以Lou/C大鼠的脾细胞作为刺激细胞 (经丝裂霉素处理 ) ,于接种前和每次接种后第 5天进行单向混合淋巴细胞反应 (MLR) ,同时对外周血T细胞凋亡和T细胞亚群CD4+ 、CD8+ 进行检测。结果　MLR结果显示 ,在LCTCV组 ,BN大鼠的脾细胞反应程度比接种前显著减弱 (P <0 .0 1) ,组间相同时点比较 ,　LCTCV组每分钟脉冲数值 (cpm值 )显著低于其他两组 (P <0 .0 1) ,在LTCV组 ,BN大鼠脾细胞的反应性显著高于LCTCV组 (P <0 0 1) ,而低于空白对照组 (P <0 0 5 ) ;在LCTCV组和LTCV组 ,外周血T细胞凋亡率于接种后显著增加 (P <0 0 1) ,并随着接种次数的增加而升高 ;CD4/CD8于接种TCV后明显减小 ,并且与cpm值的递减趋势一致。结论　T细胞疫苗可以诱导出同种异体特异性免疫耐受。通过诱导抗原反应性T细胞凋亡去除独特型T细胞克隆 ;可能在T细胞疫苗诱导特异性免疫耐受中起着关键性作用 ,CD4/CD8在一定程度上反映机体免疫耐受状态 ,CD8+

Role of T cell vaccination in inducing allogenic antigen-specific immune tolerance in rats

Objective To investigate the role of T cell vaccination in inducing allogenic antigen specific immune tolerance and itsmechanism. Methods T cell vaccination was made from spleen cells of BN rats, which were induced by Con A and challenged with the allogenic specific antigen . Normal BN rats were vaccinated intraperitoneally with LC TCV(antigen specific TCV) or LTCV(no association allogenic antigen control) or 1640 culture buffer (blank control) respectively. One way mixed lymphocyte reaction (MLR), the peripheral T cell apoptosis and CD4/CD8 ratioin peripheral blood were assayed before and after vaccination. Results MLRshowed that the immune response capability of BN rat spleen cells in LC TCV group was suppressed significantly ( P <0.01). The cpm value was lower in LTCV group than in blank control group after vaccination, but it was significantly higher in LTCV group than in LC TCV group. The percentage of peripheral T cell apoptosis was increased significantly after vaccination in LC TCV group. Theratio CD4/CD8 of peripheral blood significantly decreased after vaccinationin LC TCV group. Conclusion Antigen specific immune tolerance can be successfully induced by T cell vaccination. Induction of the apoptosis of antigen specific reactive T cell may play a critical role for T cell vaccination to induce antigen specific immune tolerance. CD4/CD8 is closely related to the generation of immunotolerance, CD8 + anti idiotypic T cell may playan important role in inducing antigen specific immune tolerance.