The development of specific immune regulatory drugs utilizing the structure and function of CD26

利用CD26的结构和功能开发特异性免疫调节药物

• 批准号: 13557039
• 负责人: MORIMOTO Chikao
• 金额: $ 10.75万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557039/
• 关键词: CD26; costimulatory molecule; DPPIV; CD4 memory T cells; p2l^<ciple>; ERK; autoioimmune diseases; p21^<cipl>; ラフト分面; CD45; チロシンリン酸化; IL-2; 細胞遊走; 共刺激シグナル

CD26 is T cell costimulatory molecule with dipeptidyl peptidase IV (DPPIV) enzyme activity located in its extracellular region. The expression of CD26 is enhanced after activation of T cells, while it is preferentially expressed on a subset of CD4+ memory T cells in the resting state. In this paper, we demonstrate that binding of the soluble anti-CD26 monoclonal antibody (mAb) 1F7 inhibits human T-cell growth and proliferation in both CD26-transfected Jurkat T-cell lines and human T-cell clones by inducing G1/S arrest, which is associated with enhancement of p21Cip1 expression. This effect depends on the DPPIV enzyme activity of the CD26 molecule. Moreover, we show that expression of p21Cip1 after treatment with the anti-CD26 mAb 1F7 appears to be induced through activation of extracellular signal-regulated kinase (ERK) pathway. These data thus suggest that anti-CD26 treatment may have potential use in the clinical setting involving activated T cell dysregulation, including autoimmune disorders and graft-vs.-host disease.

CD 26是位于其胞外区的具有二肽基肽酶IV（DPPIV）酶活性的T细胞共刺激分子。CD 26的表达在T细胞活化后增强，而其在静息状态下优先在CD 4+记忆T细胞的亚群上表达。在本文中，我们证明了可溶性抗CD 26单克隆抗体（mAb）1F 7的结合抑制人T细胞的生长和增殖，在CD 26转染的Jurkat T细胞系和人T细胞克隆诱导G1/S阻滞，这是与增强p21 Cip 1的表达。这种作用取决于CD 26分子的DPPIV酶活性。此外，我们表明，p21 Cip 1的表达后，处理与抗CD 26 mAb 1F 7似乎是通过激活细胞外信号调节激酶（ERK）途径诱导。因此，这些数据表明抗CD 26治疗可能在涉及活化T细胞失调的临床环境中具有潜在用途，包括自身免疫性疾病和移植物抗宿主病。宿主疾病

项目成果

Gines S, Marino M, Mallol J, Canela EI, Morimoto C, Callebaut C, Hovanessian A, Casado V, Lluis C, Franco R: "Regulation of epithelial and lymphocyte cell adhesion by adenosine deaminase-CD26 interaction"BiochemJ. 361. 203-209 (2002)

Gines S、Marino M、Mallol J、Canela EI、Morimoto C、Callebaut C、Hovanessian A、Casado V、Lluis C、Franco R：“腺苷脱氨酶-CD26 相互作用调节上皮细胞和淋巴细胞粘附”BiochemJ。

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Miyake-Nishijima R: "Role of Crk-associated substrate lymphocyte type in pathophysiology of rheumatoid arthritis in tax transgenic mice and humans"Arthr.And Rheum. (印刷中).

Miyake-Nishijima R：“Crk 相关底物淋巴细胞类型在 Tax 转基因小鼠和人类类风湿性关节炎病理生理学中的作用”Arthr. 和 Rheum。

Hisakawa N: "Aberrant Responsiveness to RANTES in Synovial Fluid T cells from Patients with Rheumatoid Arthritis"J. Rheumatol. (印刷中).

Hisakawa N：“类风湿性关节炎患者滑液 T 细胞对 RANTES 的异常反应”（正在出版）。

Kobayashi H: "Reduction of serum soluble CD26/DPPIV enzyme activity and its correlation with disease activity in patients with systemic lupus erythematosus"J.Rhematol. 29. 1858-1866 (2002)

Kobayashi H：“系统性红斑狼疮患者血清可溶性 CD26/DPPIV 酶活性的降低及其与疾病活动的相关性”J.Rhematol。