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通过皮下注射经体外激活的针对泪腺抗原的自体淋巴细胞在兔中诱导的自身免疫性泪腺炎和角结膜炎。

Autoimmune dacryoadenitis and keratoconjunctivitis induced in rabbits by subcutaneous injection of autologous lymphocytes activated ex vivo against lacrimal antigens.

作者信息

Thomas P B, Zhu Z, Selvam S, Samant D M, Stevenson D, Mircheff A K, Schechter J E, Song S W, Trousdale M D

机构信息

Ocular Surface Center, Department. of Ophthalmology, Doheny Eye Institute, 1450 San Pablo Street, Los Angeles, CA 90033-4682, USA.

出版信息

J Autoimmun. 2008 Sep;31(2):116-22. doi: 10.1016/j.jaut.2008.04.019. Epub 2008 Jun 4.

Abstract

Autologous peripheral blood lymphocytes (PBL), activated in a mixed cell reaction when co-cultured with purified rabbit lacrimal epithelial cells, are known to induce a Sjögren's-like autoimmune dacryoadenitis and keratoconjunctivitis when injected directly back into the donor animal's inferior lacrimal gland (LG). This study shows that autoreactive lymphocytes injected subcutaneously in a site away from the LG is capable of inducing an autoimmune disease in a rabbit. Induced disease (ID) develops more slowly, taking 4weeks as compared to 2weeks in the direct injection model. Initially, both clinical symptoms and histopathology are less pronounced than in the direct injection ID model, but later the immunocytochemistry shows the same CD4+/CD8+ ratio of 4:1 for both injection methods. The finding that lymphocytes activated against lacrimal antigens can travel or home from the injection site back to the inferior and superior LG, as well as the conjunctiva, suggests that these anatomical sites may have common epitopes that induce pathogenic CD4+ T cells that produce a Sjögren's-like syndrome.

摘要

已知自体外周血淋巴细胞(PBL)在与纯化的兔泪腺上皮细胞共培养时在混合细胞反应中被激活,当直接回注到供体动物的泪腺(LG)时,会诱发类似干燥综合征的自身免疫性泪腺炎和角结膜炎。本研究表明,在远离泪腺的部位皮下注射自身反应性淋巴细胞能够在兔体内诱发自身免疫性疾病。诱发疾病(ID)发展较慢,直接注射模型需要2周,而皮下注射需要4周。最初,临床症状和组织病理学表现都不如直接注射ID模型明显,但后来免疫细胞化学显示两种注射方法的CD4+/CD8+比值均为4:1。针对泪腺抗原激活的淋巴细胞能够从注射部位游走或归巢至泪腺上下叶以及结膜,这一发现表明这些解剖部位可能具有共同的表位,可诱导产生致病性CD4+T细胞,进而引发类似干燥综合征的综合征。

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