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.

系统性红斑狼疮 (SLE) 的特点是 B 细胞过度活跃和免疫调节 T 细胞缺陷。 CD28 抗原是一种辅助分子，可转导细胞激活的有效共刺激信号，并在绝大多数 CD4_+ T 细胞上表达。据报道，CD4_+CD28_- T细胞对无反应性诱导具有抵抗力，并对自身抗原表现出持续的反应性，表明CD4_+CD28_- T细胞参与自身免疫性疾病的发病机制。我们发现SLE患者外周血中普遍存在CD4_+ CD28_- T细胞。该T细胞亚群明亮地表达HLA-DR、IL-2受体、VLAβ链，表明该亚群位于T细胞激活级联的晚期。我们发现 CD4_+ CD28_- T 细胞表现出所选克隆的寡克隆扩增。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 细胞在体内被不明的、可能是自身的抗原激活，并参与人类 SLE 的发病机制。

项目成果

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Takeno,M. et. al.: "Autoreactive T cell clones from patients with SLE support polyclonal autoantibody production." The Journal of Immunology. (in press). (1997)

武野，M.

Suzuki,N.et.al.: "Hormones and Lupus : Defective dehydroepiandrosterone activity induces impaired interleukin-2 activity of T lymphocytes in patients with systemic lupus erythematosus." Annales de Medicine lnterne. 147. 248-252 (1996)

Suzuki,N.et.al.：“激素与狼疮：脱氢表雄酮活性缺陷会导致系统性红斑狼疮患者 T 淋巴细胞的白细胞介素 2 活性受损。”

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鈴木登: "全身性エリテマトーデス" 日本臨床皮膚科医学会雑誌. 50. 287-291 (1996)

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