自体灭活T细胞免疫后诱导Treg下调的机制

Mechanism of Treg down-regulation by immunization with attenuated activated autologous T cells

目的探讨自体灭活T细胞免疫注射后诱导体内调节性T细胞(Treg)下调的机制。方法自体T细胞体外用刀豆蛋白(ConA)刺激活化,照射灭活T细胞给小鼠进行皮下和腹腔免疫(每只小鼠5×106/次),每隔5 d免疫一次,免疫3次后检测小鼠体内Treg的数量及功能;对照组小鼠皮下注射PBS。ELISA法检测血清中抗鼠CD25抗体。免疫小鼠血清分离后经尾静脉注入未免疫小鼠体内,检测受体小鼠Treg的数量及功能变化。结果免疫小鼠体内CD4+CD25+Foxp3+Treg数量较对照组减少(P<0.01),抑制功能也显著降低(P<0.01),但血清中抗CD25的抗体增加(P<0.01)。正常小鼠接受免疫小鼠血清后,Treg的数量和抑制功能下调(P<0.01)。结论采用ConA活化的自体灭活T细胞免疫,可诱导抗CD25抗体增加,进而减少体内CD4+CD25+Foxp3+Treg细胞数量和功能。

Objective To explore the mechanism of down-regulation of regulatory T cells（Treg） by immunization with attenuated activated autologous T cells. Methods Autologous T cells were activated with ConA in vitro.Mice were immunized subcutaneously and intraperitoneally every 5 days for 3 times（5×10^6 per time for each mouse）,and the number and function of Treg were examined.PBS was subcutaneously injected for control group.Serum level of anti-mouse CD25 antibody was measured by ELISA.The number and function of Treg was detected by serum adoptive transfer and proliferation and inhibition assays. Results Compared with control group,there were less CD4^＋CD25^＋Foxp3^＋Treg in the mice after immunization（P〈0.01）,the immunosuppression ability decreased（P〈0.01）,and the level of anti-CD25 antibody increased（P〈0.01）.Adoptive transfer of serum from immunized mice to naive mice led to a significant decrease in Treg population and function in recipient mice（P〈0.01）. Conclusion Immunization with attenuated activated autologous T cells induces more anti-CD25 antibody,which may further down-regulate CD4^＋CD25^＋Foxp3^＋ Treg expansion and function in vivo.