Yoshimoto Keiko, Setoyama Yumiko, Tsuzaka Kensei, Abe Tohru, Takeuchi Tsutomu
Division of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan.
J Biomed Biotechnol. 2010;2010. doi: 10.1155/2010/509021. Epub 2010 Sep 6.
Accumulating evidence suggests that dysfunction of T cells underlies the pathogenesis of systemic lupus erythematosus (SLE). We revealed that SLE T cells produced an abnormally excessive amount of IFN-γin vitro upon stimulation through TCR, and the expression level of TCR zeta was significantly reduced. The production of IFN-γ by SLE T cells was negatively correlated with the expression level of TCR zeta. This correlation was abolished when the cells were stimulated with TPA and ionomycin, which bypass TCR and introduce signals directly into the cells, but the production of IFN-γ by SLE T cells remained abnormally elevated. Taken together, these data suggest that regulatory mechanisms not only for the expression of TCR zeta but also for the production of IFN-γ were impaired in SLE T cells. These impairments may be responsible for the aberrant responses of SLE T cells and partly involved in the development of SLE.
越来越多的证据表明，T细胞功能障碍是系统性红斑狼疮（SLE）发病机制的基础。我们发现，SLE T细胞在通过TCR刺激后，体外产生异常过量的IFN-γ，且TCR ζ的表达水平显著降低。SLE T细胞产生的IFN-γ与TCR ζ的表达水平呈负相关。当用佛波酯（TPA）和离子霉素刺激细胞时，这种相关性消失，因为它们绕过TCR并直接向细胞内传递信号，但SLE T细胞产生的IFN-γ仍异常升高。综上所述，这些数据表明，SLE T细胞中不仅TCR ζ表达的调节机制受损，IFN-γ产生的调节机制也受损。这些损伤可能是SLE T细胞异常反应的原因，并且部分参与了SLE的发病过程。
