CTLA4-Ig和IL-4诱导异种骨移植免疫耐受的体外研究

目的探讨CTLA4Ig和IL4在诱导异种骨移植免疫耐受中的作用。方法反应细胞为BALB/c小鼠脾淋巴细胞,刺激细胞为新西兰白兔血淋巴细胞,刺激抗原为兔骨上清液。采用经典的混合淋巴细胞培养法及骨上清液与淋巴细胞混合培养法作为异种骨移植的体外实验模型。在各培养液中分别加入CTLA4Ig、IL4及两者联合应用,通过测定其3HTdR掺入率,观察不同细胞因子对刺激淋巴细胞增殖的影响。结果1细胞刺激组CTLA4Ig和IL4均对淋巴细胞增殖有显著抑制作用P<0.001),CTLA4Ig与IL4联合应用并未显示出比CTLA4Ig单独应用更为明显的细胞增殖抑制作用(P>0.05)。2骨上清液刺激组:CTLA4Ig对细胞增殖无抑制作用(P>0.05),而IL4则有较为显著地细胞增殖抑制作用(P<0.05);CTLA4Ig与IL4联合应用也未产生比单独应用IL4更为明显的细胞增殖抑制作用(P>0.05)。结论CTLA4Ig对由细胞刺激产生的淋巴细胞增殖抑制效果较好,而IL4则对骨上清液刺激的细胞增殖抑制作用更好;CTLA4Ig与IL4联合应用并未产生协同抑制作用。

An investigation on the immune tolerance of bone xenograft induced by CTLA4-Ig and IL-4 in vitro

Objective To investigate the role played by CTLA4 Ig and IL 4 in the induction of immune tolerance in bone xenograft. Methods BALB/c mice spleen lymphocytes were used as responder cells, New Zealand rabbit lymphocytes as stimulator cells and bone supernatant as stimulator antigen. The mixed lymphocyte culture (MLC) and lymphocyte bone supernatant culture (MLBSC) were used as in vitro experimental models of bone xenograft; CTLA4 Ig, IL 4 and CTLA4 Ig IL 4 were added into their culture medium respectively, to examine the effect of each treatment on lymphocyte proliferation by measuring their 3H TdR incorporation rate. Results It was found that: 1) The cell proliferation was inhibited by either CTLA4 Ig or IL 4 significantly (P< 0.001) and the combined addition of CTLA4 Ig IL 4 did not appear to have stronger inhibition than CTLA4 Ig alone (P >0.05) in MLC. 2) In MLBSC, however the cell proliferation was not inhibited by CTLA4 Ig (P >0.05) but by IL 4 the result was significant(P< 0.05), and the concurrent administration of CTLA4 Ig IL 4 did not appear to have stronger inhibition than IL 4 alone either(P >0.05). Conclusion CTLA4 Ig could remarkably inhibit lymphocyte proliferation in MLC than in MLBSC; and IL 4 could be more effective in MLBSC than in MLC; the result did not show any synergetic effect of CTLA4 Ig IL 4.