B7反义肽预处理的受体树突状细胞诱导供体特异性的免疫低反应

Induction of donor-specific immune hyporesponsiveness by recipient-derived dentritic cells pretreated with B7 antisense peptide

目的探讨负载供体抗原的受体耐受性树突状细胞(DC)在器官移植慢性排异中的作用,为抗移植慢性排异提供新的途径。方法利用B7反义肽与负载供体抗原的成熟DC体外孵育,封闭表面B7分子,模拟不成熟DC,建立体外供体间接识别途径反应体系,观察其体外抑制受体T细胞增殖作用,收集两者反应后的受体T细胞与负载供体抗原或无关供体抗原的DC作混合淋巴细胞反应；或者通过以B7反义肽封闭的负载供体抗原的受体DC对受体小鼠预处理,3 d后取脾脏分离T细胞,与负载供体抗原或无关供体抗原的DC作混合淋巴细胞反应。结果B7反义肽封闭的DC具有抑制T细胞增殖的作用(P＜0．01),同时反应体系中抑制作用在B7反义肽终浓度处于10 mg/L与1 mg/L之间出现突变。与B7反义肽封闭的负载供体抗原的DC反应后的T细胞,产生对间接途径呈递的供体抗原的低反应性。结论B7反义肽封闭的DC可以抑制T细胞增殖,以此诱导针对间接途径呈递的供体抗原的特异性低反应性,从而抑制移植物慢性排异反应。

Objective To investigate the effect of the donor-pulsed recipient tolerogenic dentritic cells in the chonic rejection oftransplantation and to find a new antirejection therapy. Methods Donorpulsed recipient mature dentritic cells were incubated with B7 antisense peptide and the B7 signals were blocked to simulate the immature dentritic cells. The response system of the recipient-donor indirect pathway in vitro was established to investigate the inhibitory effect of the recipient T cell proliferation. After the reaction, the T cells were captured again and one-way mixed lymphocyte reaction was performed to analyze the response of T cells to recipient donor-or the-third-party-pulsed dentritic cells. Also the recipients were subjected to the injection of the B7 antisense peptide-blocked donor-pulsed recipient dentritic cells. After 3 days, the recipient spleen T cells were separated and one-way mixed lymphocyte reaction was performed again to analyze the response of T cells to recipient donor-or the-third-party-pulsed dentritic cells. Results B7 antisenae peptide-blocked dentritic cells had the inhibition to the T cells proliferation （P〈 0.01 ）. And in this system, the inhibition effect was significantly changed when the concentra- tion of the 137 antisense peptide was between 1 and 10 mg/L. The T cells captured after reaction to the B7 antisense peptide-blocked donor-pulsed dentritic cells were hyporesponsive to the same donor via the indirect pathway, but hyperresponsive to the third party via the indirect pathway. Conclusion B7 antisense peptide-blocked DC could inhibit the T cells proliferation. This could induce the donor-specific hyporesponse via the indirect pathway and inhibit the chronic rejection of the graft.