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Immunological tolerance regulated by the interaction between T cell and antigen-presenting cell

T 细胞与抗原呈递细胞相互作用调节免疫耐受

基本信息

批准号：
15390155
负责人：
ISHII Naoto
金额：
$ 9.86万
依托单位：
Tohoku University
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 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390155/
关键词：
Immunological tolerance CD4^+ T cell Antigen presenting cell regulatory T cells T-cell costimulatory signals T細胞自己免疫疾患 OX40リガンド

项目摘要

The presence of OX40^+ lymphocytes and OX40 ligand^+ (OX40L)^+ cells at the sites of inflammation in T cell-mediated disorders, such as autoimmunity, allergic and infectious diseases, and GVHD is well documented. These observations suggest important roles for OX40-OX40L interactions in immune disorders. CD25^+CD4^+ regulatory T (Treg) cells suppress autoinununity by controlling peripheral self-reactive T cell activation. Recently, several reports have revealed that OX40 is preferentially expressed on Treg cells in terms of mRNA and protein expression in mice. Thus we examined whether OX40-OX40L interaction may control Treg cell function that are essential for preventing autoimmunity.We found by using OX40L-deificient mice and mice overexpressing OX40L that CD25^-CD4^+ T cells became insensitive to Treg-mediated suppression when they were exposed to OX40L-expressing cells, or when they were treated with an agonistic OX40-specific monoclonal antibody. OX40 signaling could also abrogate the disease-preventing activity of Treg cells in an experimental model of inflammatory bowel disease using RAG2-deficient mice that expressed different levels of OX40L. Thus, these data show that OX40 signals can oppose Treg-mediated suppression when they are delivered directly to antigen-engaged naive T cells. Taken together, OX40 signaling directly control Treg-cell-mediated immune suppression.

在T细胞介导的疾病如自身免疫性疾病、过敏性疾病、感染性疾病和GVHD中，炎症部位存在OX 40 ^+淋巴细胞和OX 40配体^+（OX 40 L）^+细胞。这些观察结果表明OX 40-OX 40 L相互作用在免疫疾病中的重要作用。CD 25 ^+ CD 4 ^+调节性T（Treg）细胞通过控制外周自身反应性T细胞活化来抑制自身免疫。最近，一些报道显示，在小鼠中，OX 40在mRNA和蛋白表达方面优先表达在Treg细胞上。因此，我们研究了OX 40-OX 40 L相互作用是否可以控制Treg细胞功能，而Treg细胞功能对于预防自身免疫至关重要。我们通过使用OX 40 L缺陷小鼠和过表达OX 40 L的小鼠发现，当CD 25 ^-CD 4 ^+ T细胞暴露于表达OX 40 L的细胞或用激动性OX 40特异性单克隆抗体处理时，它们对Treg介导的抑制变得不敏感。在使用表达不同水平OX 40 L的RAG 2缺陷小鼠的炎症性肠病实验模型中，OX 40信号传导也可以消除Treg细胞的疾病预防活性。因此，这些数据显示，当将0X 40信号直接递送至抗原接合的幼稚T细胞时，它们可以对抗Treg介导的抑制。总之，0X 40信号传导直接控制Treg细胞介导的免疫抑制。

项目成果

期刊论文数量（62）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Kato, H., Kojima, H., Ishii, N., Hase, H., Imai, Y., Fujibayashi, T., Sugamura, K., Kobata, T.: "Essential role of OX40L on B cells in persistent alloantibody production following repeated alloimmunizations"J.Clin.Immunol.. (印刷中). (2004)

Kato, H.、Kojima, H.、Ishii, N.、Hase, H.、Imai, Y.、Fujibayashi, T.、Sugamura, K.、Kobata, T.：“OX40L 对 B 细胞在持久性中的重要作用重复同种免疫后同种抗体的产生“J.Clin.Immunol..（印刷中）。（2004）