Cross-linking of CD45 on suppressive/regulatory T cells leads to the abrogation of their suppressive activity in vitro

CD45 在抑制性/调节性 T 细胞上的交联导致其体外抑制活性的消除

• 批准号: 15390132
• 负责人: SHIMIZU Jun
• 金额: $ 9.66万
• 依托单位: National Institute for Longevity Sciences (2005)Tokyo Metropolitan Institute of Gerontology (2003-2004)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390132/
• 关键词: Aging; CD4 T cells; Immunoregulation

CD4^+CD25^+ T cells have immunoregulatory and suppressive functions, and are responsible for suppressing self-reactive cells and maintaining self-tolerance. In addition to CD4^+CD25^+ T cells, there is also some evidence that a fraction of CD4^+CD25^- T cells exhibit suppressive activity in vitro or in vivo. We have shown using aged mice that aging not only leads to a decline in the ability to mount CD4^+CD25^- T cell responses, but at the same time, renders aged CD4^+CD25^- T cells suppressive. Here we report two newly established mAbs, which could abrogate the suppressive function of aged CD4^+CD25^- T cells. These mAbs recognized the same protein, the transmembrane phosphatase CD45. Cross-linking of CD45 on aged CD4^+CD25^- T cells was required for the disruption of their suppressive activity. Surprisingly, these mAbs also abrogated the suppressive action of CD4^+CD25^+ T cells in vitro. Our results demonstrate an unexpected function of CD45 as a negative regulator neutralizing the suppressive activity of aged CD4^+CD25^- and young CD4^+CD25^+ T cells.

CD4^+ CD25^+ T细胞具有免疫调节和抑制功能，并负责抑制自反应性细胞并保持自耐受性。除了CD4^+CD25^+T细胞外，还有一些证据表明，CD4^+CD25^ - T细胞的一部分在体外或体内表现出抑制活性。我们已经使用老年小鼠表明，衰老不仅会导致固定CD4^+CD25^ - T细胞反应的能力下降，而且同时使年龄的CD4^+CD25^ - T细胞抑制了老化。在这里，我们报告了两个新建立的mAb，可以消除老化CD4^+CD25^ - T细胞的抑制作用。这些mAb识别出相同的蛋白质，即跨膜磷酸酶CD45。 CD45在老年CD4^+CD25^ - T细胞上的交联是为了破坏其抑制活性。令人惊讶的是，这些mAb还废除了体外CD4^+ CD25^+ T细胞的抑制作用。我们的结果表明，CD45的意外功能是负调节器中和陈年CD4^+CD25^ - 和Young CD4^+CD25^+T细胞的抑制活性。

项目成果

Control of autoimmune myocarditis and multi-organ inflammation by GITR^<high>, Foxp3-expressing CD25^+ and CD25^- regulatory T cells

通过 GITR^<high>、表达 Foxp3 的 CD25^ 和 CD25^- 调节性 T 细胞控制自身免疫性心肌炎和多器官炎症

• 发表时间: 2006
• 期刊: J.Immunol. (In press)
• 作者: Ono;M.
• 通讯作者: M.

Suri A, Shimizu J, et al.: "Regulation of autoimmune diabetes by non-islet-specific T cells-a role for the glucocorticoid-induced TNF receptor."Eur.J.Immunol.. 34. 447-454 (2004)

Suri A、Shimizu J 等人：“非胰岛特异性 T 细胞对自身免疫糖尿病的调节 - 糖皮质激素诱导的 TNF 受体的作用。”Eur.J.Immunol.. 34. 447-454 (2004)

Control of atuoimmune myocarditis and multi-organ inflammation by GITR^high,Foxp-expressing CD25^+ regulatory T cells

通过 GITR^high、表达 Foxp 的 CD25^ 调节性 T 细胞控制自身免疫性心肌炎和多器官炎症

• 发表时间: 2006
• 期刊: J.Immunol. 176
• 作者: Ono;M.
• 通讯作者: M.

老化に伴う免疫抑制性CD4T細胞の出現

随着衰老出现免疫抑制性 CD4T 细胞

• 发表时间: 2004
• 期刊: 基礎老化研究 28
• 作者: Kaminuma;O.;Kitamura;F.;Kiramura;N.;Miyagishi;M.;Taira;K.;Yamamoto;K.;Miura;O.;Miyatake;S.;Noriko M Tsuji;辻 典子;Bian Y;Shimizu J;清水 淳;清水 淳
• 通讯作者: 清水 淳

Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells.

• DOI: 10.1084/jem.20050940
• 发表时间: 2005-10-03
• 期刊: JOURNAL OF EXPERIMENTAL MEDICINE
• 影响因子: 15.3
• 作者: Ko, K;Yamazaki, S;Nakamura, K;Nishioka, T;Hirota, K;Yamaguchi, T;Shimizu, J;Nomura, T;Chiba, T;Sakaguchi, S
• 通讯作者: Sakaguchi, S