格雷夫氏病是一种自体免疫疾病，患者体内的免疫系统会攻击自己的甲状腺，导致甲状腺肿大。患者的单侧和双侧突眼为该病的主要病征。
加州大学洛杉矶分校的研究人员发现了新的线索，可以解释为什么这种疾病会攻击眼睛后方的肌肉组织，使患者的眼睛突出。
研究人员发现，从格雷夫氏病患者身上取得的T细胞中，含有异常过量的自体抗体的受体。论文作者表示，目前还不知道为什么格雷夫氏病会制造攻击身体的抗体。由于T 细胞是免疫系统带领攻击的主角，所以研究人员假设T细胞与这种抗体有密切的关连性。
研究人员发现，几乎所有格雷夫氏病患者都有这种抗体，新抗体会与T细胞上过多的受体结合，模拟IGF-1激素的作用，刺激细胞生长且抑制正常细胞死亡。这个机制会延长老的T细胞的寿命，因此刺激身体攻击自己的组织，引起一连串的自体免疫事件。这项研究结果发表于3月1日的《免疫学杂志》（Journal of Immunology）中。
部分英文原文：
The Journal of Immunology, 2007, 178: 3281-3287.
Copyright © 2007 by The American Association of Immunologists, Inc.
Aberrant Expression of the Insulin-Like Growth Factor-1 Receptor by T Cells from Patients with Graves’ Disease May Carry Functional Consequences for Disease Pathogenesis1
Raymond S. Douglas*,,, Andrew G. Gianoukakis*,, Shweta Kamat* and Terry J. Smith2,*,,
* Department of Medicine, Division of Molecular Medicine, Harbor-University of California Los Angeles Medical Center, and Los Angeles Biomedical Research Institute, Torrance, CA 90502; Jules Stein Eye Institute, Los Angeles, CA 90095; and David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095
Graves’ disease (GD), an autoimmune process involving thyroid and orbital tissue, is associated with lymphocyte abnormalities including expansion of memory T cells. Insulin-like growth factor receptor-1 (IGF-1R)-bearing fibroblasts overpopulate connective tissues in GD. IGF-1R on fibroblasts, when ligated with IgGs from these patients, results in the expression of the T cell chemoattractants, IL-16 and RANTES. We now report that a disproportionately large fraction of peripheral blood T cells express IGF-1R (CD3+IGF-R+). CD3+IGF-1R+ T cells comprise 48 ± 4% (mean ± SE; n = 33) in patients with GD compared with 15 ± 3% (n = 21; p < 10–8) in controls. This increased population of IGF-1R+ T cells results, at least in part, from an expansion of CD45RO+ T cells expressing the receptor. In contrast, the fraction of CD45RA+IGF-1R+ T cells is similar in GD and controls. T cells harvested from affected orbital tissues in GD reflect similar differences in the proportion of IGF-1R+CD3+ and IGF-1R+CD4+CD3+ cells as those found in the peripheral circulation. GD-derived peripheral T cells express durable, constitutive IGF-1R expression in culture and receptor levels are further up-regulated following CD3 complex activation. IGF-1 enhanced GD-derived T cell incorporation of BrdU (p < 0.02) and inhibited Fas-mediated apoptosis (p < 0.02). These findings suggest a potential role for IGF-1R displayed by lymphocytes in supporting the expansion of memory T cells in GD.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was funded in part by Grants EY016339 (to R.S.D.), RR017304 (to A.G.G.), EY008976, EY011708, and DK063121 (to T.J.S.), and RR00425 from the National Institutes of Health. We gratefully acknowledge generous support from Steve and Kathleen Flynn and the Bell Charitable Foundation.
2 Address correspondence and reprint requests to Dr. Terry J. Smith, Division of Molecular Medicine, Harbor-University of California Los Angeles Medical Center, Building C-2, 1124 West Carson Street, Torrance, CA 90502. E-mail address: tjsmith@ucla.edu
3 Abbreviations used in this paper: IGF-1R, insulin-like growth factor receptor-1; GD, Graves’ disease; TAO, thyroid-associated ophthalmopathy; MFI, mean fluorescent intensity; 7-AAD, 7-aminoactinomycin D.
