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

CD4^CD28^-T细胞亚群在系统性红斑狼疮患者中的作用

• 批准号: 07670547
• 负责人: SUZUKI Noboru
• 金额: $ 1.54万
• 依托单位: ST.MARIANNA UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670547/
• 关键词: CD28; accessory molecule; Tlymphocytes; helper T cells; systemic lupus erythematosus; oligoclonal; activation; HLA-DR; T細胞; アクセサリーシグナル; CD28分子; ヘルパー機能

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.

全身性红斑狼疮（SLE）的特征是B细胞多动和免疫调节T细胞的缺陷。 CD28抗原是一种辅助分子，可传递有效的costimulation信号，以用于细胞激活，并在绝大多数CD4_+ T细胞上表达。据报道，CD4_+CD28_- T细胞对厌食诱导是难治性的，并显示出对自抗原的持续反应性，这表明CD4_+CD28_- T细胞参与了自身免疫性疾病的发病机理。我们发现SLE患者的外周血中CD4_+ CD28_- T细胞在外周血中普遍存在。该T细胞子集表达HLA-DR，IL-2受体，Vlabeta链明亮，表明该子集位于T细胞活化级联的晚期。我们发现CD4_+ CD28_- T细胞表现出所选克隆的寡克隆膨胀。此外，CD4_+ CD28_- T细胞自发产生大量IL-6。这些结果表明，SLE CD4_+CD28_- T细胞已通过体内未鉴定的，可能是自我抗原激活，并参与了人SLE的发病机理。

项目成果

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