NOD小鼠胸腺细胞TCR介导的信号通路缺陷

Defect of TCR-mediated signal pathway of thymocytes in autoimmune non-obese diabetic mouse thymus

目的 进一步研究NOD小鼠T细胞应答改变机理。方法 用抗TCR抗体、ConA激活NOD小鼠胸腺细胞 ,分析TCR介导的信号通路的水平。结果 与Balb c小鼠胸腺细胞相比 ,抗TCR抗体诱导的增殖应答较弱 ,与年龄及NOD胸腺CD4 +CD8- 和CD4 - CD8+SP细胞有关 ;rIL 2能部分恢复对TCR抗体应答的缺乏。NOD小鼠对PMA +IONO和PMA +anti TCR mAb应答正常 ,但对anti TCRmAb +IONO应答缺乏。结论 与年龄有关的NOD小鼠胸腺细胞对TCR抗体应答的缺乏与T细胞激活时上游PKC信号通路的缺乏有关。

Objective To study the mechanism responsible for T cell alterations in NOD mice. Methods We examined whether a defect exists in the thymus of NOD mice at the level of TCR mediated signaling after activation by anti TCR and ConA. Results Thymocytes from NOD mice respond weakly to anti TCR induced proliferation, compared with thymocytes from Balb/c mice. This defect correlates with the age, and both NOD CD4 +CD8 - and CD4 -CD8 + mature thymic T cells respond poorly to anti TCR. The defect can be partially reversed by the addition of rIL 2 to NOD thymocytes. In contrast to their low proliferative response to anti TCR, NOD thymocytes respond normally to the combinations of PMA plus the Ca 2+ ionophore ionomycin and PMA plus anti TCR but weakly to anti TCR plus ionomycin. Conclusion The age related NOD thymocyte unresponsiveness to anti TCR results from a defect in the signaling pathway of T activation that occurs upstream of protein kinase C activation.