Daniel D, Gill R G, Schloot N, Wegmann D
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver 80262, USA.
Eur J Immunol. 1995 Apr;25(4):1056-62. doi: 10.1002/eji.1830250430.
T cells are known to play an important role in beta cell destruction in the nonobese diabetic (NOD) mouse model of Type I diabetes and islet-specific T cell clones have been demonstrated to be capable of adoptive transfer of diabetes. One important issue involves the identity of beta cell antigens that are recognized by nominally islet cell-specific T cell clones. We have previously reported that insulin-specific T cells are a predominant component of islet-specific T cells isolated from islet infiltrates of pre-diabetic NOD mice. In this report we examine six independently derived insulin-specific T cell clones established from islet infiltrates of pre-diabetic NOD mice in detail. All six clones were found to be specific to a region of the insulin molecule defined by a synthetic peptide encompassing residues 9-23 of the B chain. Despite this restricted specificity, each member of this panel exhibited a distinct receptor specificity defined either by V beta usage or antigen fine specificity. Five clones produced interferon (IFN)-gamma but not interleukin (IL)-4, placing them in the T helper type 1 (TH1)-like category whereas one clone produced both IL-4 and IFN-gamma, a characteristic of TH0 cells. All six clones were capable of either acceleration of diabetes in young NOD mice or adoptive transfer to NODscid mice. Taken together, these results suggest that spontaneously arising insulin-specific T cells participate in beta cell destruction during development of diabetes in NOD mice.
已知T细胞在I型糖尿病非肥胖糖尿病（NOD）小鼠模型的β细胞破坏中起重要作用，并且胰岛特异性T细胞克隆已被证明能够进行糖尿病的过继转移。一个重要问题涉及名义上胰岛细胞特异性T细胞克隆所识别的β细胞抗原的身份。我们之前报道过，胰岛素特异性T细胞是从糖尿病前期NOD小鼠的胰岛浸润物中分离出的胰岛特异性T细胞的主要成分。在本报告中，我们详细研究了从糖尿病前期NOD小鼠的胰岛浸润物中建立的六个独立衍生的胰岛素特异性T细胞克隆。发现所有六个克隆都对胰岛素分子的一个区域具有特异性，该区域由包含B链9 - 23位残基的合成肽所定义。尽管具有这种受限的特异性，但该组中的每个成员都表现出由Vβ使用情况或抗原精细特异性所定义的独特受体特异性。五个克隆产生干扰素（IFN）-γ但不产生白细胞介素（IL）-4，将它们归类为1型辅助性T（TH1）样细胞，而一个克隆同时产生IL-4和IFN-γ，这是TH0细胞的特征。所有六个克隆都能够加速年轻NOD小鼠的糖尿病进程或过继转移到NODscid小鼠。综上所述，这些结果表明自发产生的胰岛素特异性T细胞在NOD小鼠糖尿病发展过程中参与β细胞破坏。
