负性协同刺激分子B7-H4在小鼠树突状细胞上的表达及其生物学意义

目的 探讨B7-H4分子在小鼠树突状细胞分化发育过程中的表达及其在T细胞活化中的作用.方法 采用GM-CSF和IL-4联合方案体外诱导小鼠髓系树突状细胞(DCs);采用流式细胞术检测未成熟DCs、成熟DCs以及IL-10诱导的DCs表面B7-H4分子的表达;采用3H-TdR掺入试验和抗B7-H4单抗(McAb)阻断试验分析DCs表达的B7-H4分子对T淋巴细胞的共刺激效应.结果 经GM-CSF和IL-4联合方案体外诱导的未成熟DCs较高水平表达B7-H4,在IL-10作用下B7-H4表达进一步上调,经TNF-α刺激成熟后,B7-H4的表达显著下调,不同功能状态下DCs表面B7-H4分子均可抑制T细胞的增殖,但以未成熟DCs、IL-10诱导的DCs表面B7-H4分子的抑制作用更为显著.结论 不同功能状态下的DCs均有B7-H4分子的表达,处于抑制状态下的DCs通过高表达B7-H4介导免疫不应答效应.

Expressions of B7-H4 in mouse myeloid dendritic cells and its role in activation of T lymphocytes

Objective To study the role of B7-H4 on the surface of murine DCs in mediating T cell activation.Methods Mouse myetoid dendritic cells(DCs)were generated from bone marrow in vitro using GM-CSF and IL-4,and further stimulation with TNF-α or IL-10 for 48 h,respectively.Expressions of B7-H4 on DCs were analyzed by FCM.3H-thymidine incorporation test was used to detect the T cell proliferation stimulated by DCs with or without blocking B7-H4 by McAb.respectively.Results 5-6 d DCs in our system can be regarded as imDCs.B7-H4 was expressed moderately on imDCs,and could be markedly upregulated by IL-10,and be markedly down-regulated by TNF-α.3H-thymidine incorporation test showed that blockade of B7-H4 on imDCs and IL-10-treated DCs resulted in enhancement of T cell proliferation signiticantly.When T cells encountered with mDCs.B7-H4 blockade could not markedly enhance the T cells proliferation as seen in inhibitory DCs.Conclusion Expression of B7-H4 on inhibitory DCs might contribute to its immunoinhibitory effect.