格雷夫氏病是一種自體免疫疾病,，患者體內(nèi)的免疫系統(tǒng)會(huì)攻擊自己的甲狀腺,，導(dǎo)致甲狀腺腫大,?；颊叩膯蝹?cè)和雙側(cè)突眼為該病的主要病征。
加州大學(xué)洛杉磯分校的研究人員發(fā)現(xiàn)了新的線索,，可以解釋為什么這種疾病會(huì)攻擊眼睛后方的肌肉組織,，使患者的眼睛突出。
研究人員發(fā)現(xiàn),，從格雷夫氏病患者身上取得的T細(xì)胞中,，含有異常過量的自體抗體的受體。論文作者表示,，目前還不知道為什么格雷夫氏病會(huì)制造攻擊身體的抗體,。由于T 細(xì)胞是免疫系統(tǒng)帶領(lǐng)攻擊的主角，所以研究人員假設(shè)T細(xì)胞與這種抗體有密切的關(guān)連性,。
研究人員發(fā)現(xiàn),，幾乎所有格雷夫氏病患者都有這種抗體，新抗體會(huì)與T細(xì)胞上過多的受體結(jié)合,，模擬IGF-1激素的作用,，刺激細(xì)胞生長且抑制正常細(xì)胞死亡。這個(gè)機(jī)制會(huì)延長老的T細(xì)胞的壽命,，因此刺激身體攻擊自己的組織,，引起一連串的自體免疫事件。這項(xiàng)研究結(jié)果發(fā)表于3月1日的《免疫學(xué)雜志》（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: [email protected]
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.
