诱导人T细胞对猪抗原免疫耐受的体外实验研究

An experimental study on the in vitro induced immune tolerance of human T cell to porcine antigen presenting cells

目的：探讨诱导人Ｔ细胞对猪抗原免疫耐受的状况。方法：通过建立人幼稚淋巴细胞与猪抗原递呈细胞混合培养模型，以淋巴细胞增殖实验及毒性实验、ＤＮＡ分析、淋巴细胞表面标志检测等手段，观测了幼稚淋巴细胞分化、发育过程中对异种负调细胞疫苗初次接触与再次刺激的免疫应答状况的变化。结果：发现在体外，异种负调细胞疫苗能诱导人幼稚及成熟Ｔ细胞产生免疫耐受；辅助信号系统耐受在诱导过程中起着至关重要的作用。结论：提示在该系统中免疫耐受发生的机理是克隆排除与免疫无应答。

Objective:To investigate the possibility and mechanism of the tolerance of human T cell to porcine antigen presenting cells,the present study tried to prepare a kind of down regulating cell vaccine(DRCV) and establish an in vitro novel model of immune tolerance,i.e.,mixed immature lymphocyte porcine APC reaction.Methods:Based on this model,the lymphocyte proliferation,cytotoxicity,apoptosis,immunohistochemistry and FACS were used for analyze of immature T cell differentiation,the reaction of immature T cell to both primary and secondary APC stimulation,and the apoptosis of reactive T cells.Results:The results showed that:DRCV presented a very low level of CD86 expression,but the normal level of MHC Ⅱ;DRCV could induce the antigen specific immune tolerance of both immature and mature T cells and the underlying mechanism of this kind of immune tolerance was of anergy and clonal deletion occurred during the secondary encounter between human memorial T cells and the xeno APC.Conclusion:According to the above data, propose that the expression of TCR on immature T cell is regulated by antigens;the co stimulatory signals play critical roles in the induction of both immature and matrue T cell immune tolerance;and clonal deletion and unresponsiveness is responsible for the antigen specific immune tolerance.