Chang J C, Linarelli L G, Laxer J A, Froning K J, Caralli L L, Brostoff S W, Carlo D J
Immune Response Corporation, Carlsbad, CA 92008, USA.
J Autoimmun. 1995 Apr;8(2):221-34. doi: 10.1006/jaut.1995.0017.
T cell clones reactive to beta-cell antigens prepared from different species were established in order to identify putative pathogenic T cells in human IDDM. We were able to generate T cell clones from patients, but not from controls, reactive specifically to the insulin secretory enriched fraction (ISG) of a rat insulinoma RIN cell line. This finding is suggestive of an in vivo priming by the antigen(s). To examine the relevance of these T cell clones in the pathogenesis of IDDM, we studied their cytokine profile. T cell clones from the newly onset patients had a Th1 cytokine profile, while those from the prediabetic patient were of the Th2 subtype. This segregation suggests that RIN-ISG contains antigen(s) involved in the pathogenesis of this disease, since IDDM is considered a cell-mediated or Th1 disease. Since two of these clones also responded to a hamster insulinoma cell line HIT, at least two antigens in RIN-ISG could be defined by this panel of T cell clones. Examination of CDR3 sequences confirmed the clonality of the dual-reactive T cell clones. The finding of HIT-reactive cells in IDDM patients may be useful in efforts to identify prediabetic patients for immune intervention. Dual reactivity may provide a better prognosis than single reactivity. In contrast to T cell clones reactive to insulinomas, T cell clones reactive to normal human ISG were not found after over 200 clones were screened. In addition, RIN-ISG specific clones did not respond to either normal human or rat ISG, suggesting that IDDM antigens are below detectable levels in normal beta cells.
为了鉴定人类胰岛素依赖型糖尿病（IDDM）中假定的致病性T细胞，建立了对来自不同物种的β细胞抗原具有反应性的T细胞克隆。我们能够从患者而非对照中产生对大鼠胰岛素瘤RIN细胞系的胰岛素分泌富集部分（ISG）具有特异性反应的T细胞克隆。这一发现提示抗原在体内引发了免疫反应。为了研究这些T细胞克隆在IDDM发病机制中的相关性，我们研究了它们的细胞因子谱。新发病患者的T细胞克隆具有Th1细胞因子谱，而糖尿病前期患者的T细胞克隆属于Th2亚型。这种区分表明RIN-ISG含有参与该疾病发病机制的抗原，因为IDDM被认为是一种细胞介导的或Th1型疾病。由于其中两个克隆也对仓鼠胰岛素瘤细胞系HIT有反应，因此通过这组T细胞克隆可以确定RIN-ISG中的至少两种抗原。对CDR3序列的检测证实了双反应性T细胞克隆的克隆性。在IDDM患者中发现对HIT有反应的细胞可能有助于识别糖尿病前期患者以便进行免疫干预。双反应性可能比单反应性具有更好的预后。与对胰岛素瘤有反应的T细胞克隆不同，在筛选了200多个克隆后未发现对正常人ISG有反应的T细胞克隆。此外，RIN-ISG特异性克隆对正常人或大鼠的ISG均无反应，这表明IDDM抗原在正常β细胞中的水平低于可检测水平。
