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.

CD 4 ^+ CD 25 ^+ T细胞具有免疫调节和抑制功能，并负责抑制自身反应细胞和维持自身耐受。除了CD 4 ^+ CD 25 ^+ T细胞外，还有一些证据表明，一部分CD 4 ^+ CD 25 ^- T细胞在体外或体内表现出抑制活性。我们已经用老年小鼠证明，衰老不仅导致产生CD 4 ^+ CD 25 ^- T细胞应答的能力下降，同时还使衰老的CD 4 ^+ CD 25 ^- T细胞具有抑制性。在此，我们报道了两种新建立的单克隆抗体，它们可以消除衰老的CD 4 ^+ CD 25 ^- T细胞的抑制功能。这些单克隆抗体识别相同的蛋白质，跨膜磷酸酶CD 45。老化的CD 4 ^+ CD 25 ^- T细胞上的CD 45交联是破坏其抑制活性所必需的。令人惊讶的是，这些单克隆抗体在体外也消除了CD 4 ^+ CD 25 ^+ T细胞的抑制作用。我们的研究结果表明，CD 45作为一种负调节因子，具有一种意想不到的功能，可以中和衰老的CD 4 ^+ CD 25 ^-和年轻的CD 4 ^+ CD 25 ^+ T细胞的抑制活性。

项目成果

加齢と免疫

衰老与免疫力

• 发表时间: 2005
• 期刊: 生涯教育シリーズ67 日本医師会雑誌特別号「わかりやすい免疫疾患」 (in press)
• 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
• 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.

用激动性抗GITR mAb治疗晚期肿瘤及其对肿瘤浸润Foxp3+CD25+CD4+调节T细胞的影响。

• 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

CD4+CD25+Foxp3+ T cells and CD4+CD'25-Foxp3+ T cells in aged mice

• DOI: 10.4049/jimmunol.176.11.6586
• 发表时间: 2006-06-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Nishioka, Tomohisa;Shimizu, Jun;Sakaguchi, Shimon
• 通讯作者: Sakaguchi, Shimon

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)

加齢と免疫「わかりやすい免疫疾患」生涯教育シリーズ67

衰老与免疫 《通俗易懂的免疫疾病》终身教育系列67

• 发表时间: 2005
• 期刊: 日本医師会雑誌特別号
• 作者: Ko;K.;清水淳
• 通讯作者: 清水淳