Role of CD4^+CD28^-T cell subset in patients with Systemic Lupus Erythematosus

系统性红斑狼疮（SLE）以B细胞过度活跃和免疫调节性T细胞缺陷为特征。CD28抗原是一种辅助分子，可转导细胞激活的强效共刺激信号，在绝大多数CD4_+ T细胞上表达。有报道称，CD4_+CD28_- T细胞对能量诱导不耐受，对自身抗原表现出持续的反应性，提示CD4_+CD28_- T细胞参与自身免疫性疾病的发病机制。我们发现CD4_+ CD28_- T细胞在SLE患者外周血中普遍存在。该T细胞亚群明亮地表达HLA-DR、IL-2受体、VLAbeta链，表明该亚群处于T细胞激活级联的后期。我们发现CD4_+ CD28_- T细胞表现出选择克隆的寡克隆扩增。此外，CD4_+ CD28_- T细胞自发产生大量IL-6。这些结果提示SLE CD4_+CD28_- T细胞在体内被未知的、可能是自身的抗原激活，参与了SLE的发病过程。

Systemic lupus erythematosus (SLE) is characterized by B cell hyperactivity and defects of immunoregulatory T cells. CD28 antigen is an accessory molecule, that transduces a potent costimulatory signal for cell activation, and is expressed on the vast majority of CD4_+ T cells. It has been reported that CD4_+CD28_- T cells were refractory to anergy induction and showed sustained reactivity to the self antigen, suggesting involvement of CD4_+CD28_- T cells in the pathogenesis of autoimmune diseases. We found that CD4_+ CD28_- T cells are prevalent in peripheral blood in patients with SLE.This T cell subset expressed HLA-DR,IL-2 receptor, VLAbeta chain brightly, indicating that this subset locates in a late stage of T cell activation cascade. We found that CD4_+ CD28_- T cells exhibited oligoclonal expansion of the selected clones. In addition, CD4_+ CD28_- T cells produced large amounts of IL-6 spontaneously. These results suggest that SLE CD4_+CD28_- T cells have been activated by unidentified, possibly self, antigen in vivo and participate in the pathogenesis of human SLE.