Jungheim K, Caspar G, Usadel K H, Schumm-Draeger P M
Department of Medicine I, Center of Internal Medicine, J.W. Goethe-University, Frankfurt, Germany.
Thyroid. 2004 Jan;14(1):3-11. doi: 10.1089/105072504322783786.
Homing of lymphocytes is an important factor with respect to the initiation of the autoimmune process in Graves' disease (GD). As previously shown, human lymphocytes, particularly of intrathyroidal origin, derived from patients with GD, are able to migrate into normal xenotransplanted thyroid tissue and induce functional and histological changes. The aim of this study was to investigate the effect of LFA-1 and ICAM-1 antibodies on the homing of lymphocytes of different origin into xenografted human thyroid tissue.
Eighty-five nude mice bearing 8-week-old xenografts of normal human thyroid tissue were treated twice with anti-CD 54 (anti-ICAM-1), anti-CD 11a (anti-LFA-1), a combination of both, or, serving as controls, iso-antibodies without specific binding capacity or saline. Thereafter, intrathyroidal (ITL) or peripheral blood lymphocytes (PBL) obtained from 4 patients with GD or saline were injected into the animals (i.v., 0.2 mL, 10(6) cells). After 48 hours the mice were sacrificed and transplants as well as mice thyroids were examined by immunohistochemical staining with Ki67, CD3, HLA-II (DAKO, Hamburg), IgG, CD44, ICAM-1, and VCAM-1 (Immunotech, Hamburg).
Pretreatment with anti-ICAM-1 and anti-LFA-1 decreased lymphocyte homing (CD3-staining), and expression of HLA-II, IgG, CD44, and VCAM-1 in the transplants.
Our data show that [ICAM-1/LFA-1 stimulated (induced)] lymphocyte homing and subsequently thyrocyte proliferation are inhibited by ICAM-1 and LFA-1 antibodies in xenotransplanted thyroid tissue. This suggests that ICAM1 and LFA-1 play an important role in the early steps of autoimmune thyroid disease. The inhibition/suppression of ICAM-1 and LFA-1 interaction by respective antibodies, as demonstrated in the present study, may provide a new concept for prophylaxis and therapy.
淋巴细胞归巢是格雷夫斯病（GD）自身免疫过程启动的一个重要因素。如先前所示，来自GD患者的人淋巴细胞，尤其是甲状腺内来源的淋巴细胞，能够迁移到正常异种移植的甲状腺组织中并诱导功能和组织学变化。本研究的目的是调查淋巴细胞功能相关抗原-1（LFA-1）和细胞间黏附分子-1（ICAM-1）抗体对不同来源淋巴细胞归巢至异种移植人甲状腺组织的影响。
85只裸鼠移植了8周龄正常人甲状腺组织异种移植物，分别用抗CD 54（抗ICAM-1）、抗CD 11a（抗LFA-1）、两者组合进行两次处理，或作为对照，用无特异性结合能力的同种抗体或生理盐水处理。此后，将从4例GD患者获得的甲状腺内淋巴细胞（ITL）或外周血淋巴细胞（PBL）或生理盐水静脉注射到动物体内（0.2 mL，10⁶个细胞）。48小时后处死小鼠，通过用Ki67、CD3、人类白细胞抗原II类分子（HLA-II，丹麦达科公司，汉堡）、免疫球蛋白G（IgG）、CD44、ICAM-1和血管细胞黏附分子-1（VCAM-1，免疫技术公司，汉堡）进行免疫组织化学染色来检查移植物以及小鼠甲状腺。
用抗ICAM-1和抗LFA-1预处理可减少淋巴细胞归巢（CD3染色），并降低移植物中HLA-II、IgG、CD44和VCAM-1的表达。
我们的数据表明，ICAM-1和LFA-1抗体可抑制异种移植甲状腺组织中[ICAM-1/LFA-1刺激（诱导）的]淋巴细胞归巢以及随后的甲状腺细胞增殖。这表明ICAM1和LFA-1在自身免疫性甲状腺疾病的早期阶段起重要作用。如本研究所示，用相应抗体抑制ICAM-1和LFA-1的相互作用可能为预防和治疗提供一个新的概念。
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