Evidence that the T cell repertoire of normal rats contains cells with the potential to cause diabetes. Characterization of the CD4+ T cell subset that inhibits this autoimmune potential.
Evidence that the T cell repertoire of normal rats contains cells with the potential to cause diabetes. Characterization of the CD4+ T cell subset that inhibits this autoimmune potential.
复制标题
正常大鼠的T细胞库中含有引起糖尿病的潜力的细胞。 CD4+ T细胞子集的表征抑制了这种自身免疫电位。
DOI：
10.1084/jem.177.3.627
复制
发表时间：
1993-03-01
影响因子：
15.3
通讯作者：
Mason, D
中科院分区：
文献类型：
--
作者：
Fowell, D;Mason, D
在一个正常的非自身免疫性大鼠品系中，通过使用成年胸腺切除术和亚致死伽马辐射使动物相对T细胞缺陷诱导糖尿病。所有雄性大鼠和70%的雌性大鼠出现急性综合征，伴有严重的体重减轻和高血糖。这些淋巴细胞减少大鼠的糖尿病与涉及CD4+和CD8+ T细胞和巨噬细胞的广泛胰岛素炎相关。CD8+ T细胞对糖尿病的发展至关重要，而不是胰岛素。通过注射从健康的同基因供体中分离的cd45rclo T细胞受体α / β + RT6+ Thy-1- OX-40-的特定CD4+ T细胞亚群，可完全预防自身免疫性糖尿病和胰岛素。这种保护性表型的细胞约占胸导管淋巴细胞的5%，它们被发现有助于二抗反应，并在体外激活时产生白细胞介素2 （IL-2）和IL-4，但不产生干扰素γ。这些数据为大鼠正常免疫系统中存在自身反应性T细胞提供了证据，并揭示了在完整的动物中，这些细胞被其他T细胞阻止表达自身反应性电位。
Diabetes was induced in a normal nonautoimmune rat strain by rendering the animals relatively T cell deficient using a protocol of adult thymectomy and sublethal gamma irradiation. All male rats and 70% of females developed an acute syndrome with severe loss of weight and hyperglycemia. Diabetes in these lymphopoenic rats was associated with extensive insulitis involving CD4+ and CD8+ T cells and macrophages. The CD8+ T cells were essential for the development of diabetes but not insulitis. The autoimmune diabetes and insulitis were completely prevented by the injection of a particular CD4+ T cell subset, isolated from healthy syngeneic donors, of the phenotype CD45RClow T cell receptor alpha/beta+ RT6+ Thy-1- OX-40-. Cells of this protective phenotype, which make up about 5% of thoracic duct lymphocytes, were found to provide help for secondary antibody responses and produce interleukin 2 (IL-2) and IL-4, but no interferon gamma, on in vitro activation. These data provide evidence for the presence of autoreactive T cells in the normal immune system of the rat and reveal that in the intact animal these cells are prevented from expressing their autoreactive potential by other T cells.