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Immune Regulation of Extrathymic T (NK1.1^+T) Cells in Parasitic Infection

寄生虫感染中胸腺外 T (NK1.1^ T) 细胞的免疫调节

基本信息

批准号：
08670276
负责人：
SEKIKAWA Hiroho
金额：
$ 1.34万
依托单位：
NIIGATA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670276/
关键词：
Hepatic lymphocyte Extrathymic T cells Host defense Murine Malaria Self-reactive forbidden clones Cytotoxicity against malaria infected red blood cells Leishmaniasis Visceral larve migrans 原虫感染ネズミマラリア蠕虫感染イヌ蛔虫 IL-4産生細胞サイトカイン産生

项目摘要

In a series of recent studies, we have demonstrated that the liver is an important immune organs that produces extrathymic T cells in mice and humans. These T cells are distinguished from thymus-derived T cells by many properties. Some of these properties include the intermediate density of TCR-CD3 complex on their surface and constitutive expression of interleukin-2Rbeta-chain.The development of protective immunity to parasitic infection requires the presence of T cells. In this project, we investigated the role of extrathyinic T cells in mice during infection with murine malaria (P.yoelli), Leishmania (L.major) and Ascaris larvae (T.canis).1) Visceral larva migrans model In early phase of T.canis infection (on day 1), unique population of hepatic T cells were observed, i.e., double-positive (DP) CD4^+CD8^+ cells. The proportion of extrathymic T cells was also elevated therafter.2) Leishmaniasis model In mice infected with L.major, the levels of extrathymic T cells in the liver increased. The produciblity of IL-4 in these T cells elevated in the liver. These observations indicate that the induction of Th2 type immune response is dominant in murine Leishmaniasis.3) Murine malaria model Expansion of extrathymic T cells were observed with flowcytometric analysis of lymphocytes from liver, spleen and thymus. They possessed self-reactive forbidden clones and cytotoxicity against parasitized RBC.Deletion of TL-2Rbeta^+ cells resulted in early exacerbation of infection of the non-lethal strain malaria. These data indicate the extrathymic T cells play a role during the erythrocytic stage of the rodent malaria infection.These results suggest that the expanding extrathymic T cells in various organs play an important role of protective immunity during parasitic infection.

在最近的一系列研究中，我们已经证明肝脏是小鼠和人类产生胸腺外T细胞的重要免疫器官。这些T细胞与胸腺来源的T细胞的许多特性不同。这些特性包括其表面的中等密度的TCR-CD 3复合物和白细胞介素-2R β链的组成性表达。在本项目中，我们研究了小鼠在感染鼠疟疾（约氏疟原虫）、利什曼原虫（利什曼原虫）和蛔虫幼虫（犬蛔虫）期间胸腺外T细胞的作用。1）内脏幼虫移行模型在犬蛔虫感染的早期阶段（第1天），观察到独特的肝脏T细胞群，即，双阳性（DP）CD 4 ^+ CD 8 ^+细胞。2）利什曼病模型感染小鼠肝脏中胸腺外T细胞水平升高。在肝脏中，这些T细胞中IL-4的产生量升高。3）小鼠疟疾模型用流式细胞仪检测小鼠胸腺、脾脏和肝脏中T淋巴细胞的增殖情况。它们具有自身反应性的禁忌克隆和抗寄生红细胞的细胞毒性。TL-2 R β ^+细胞的缺失导致非致死性疟疾株感染的早期加重。这些结果表明，在疟原虫感染的红内期，胸腺外T细胞发挥了重要作用，说明在疟原虫感染过程中，胸腺外T细胞在各器官中的扩增发挥了重要的保护性免疫作用。