小鼠自发性眼自身免疫表达的转基因T细胞受体对视网膜的特异性：剖析葡萄膜炎机制的一种工具

Title:Spontaneous Ocular Autoimmunity in Mice Expressing a Transgenic T Cell Receptor Specific to Retina: A Tool to Dissect Mechanisms of Uveitis

Volume: 15 Issue: 6

Author(s): R. Horai, W.P. Chong, R. Zhou, J. Chen, P.B. Silver, R.K. Agarwal and R.R. Caspi

Affiliation:

关键词: 自身免疫，葡萄膜炎，EAU，动物模型，Th1，Th17

摘要: The “classical” EAU model induced by immunization of mice with the retinal protein IRBP or its peptides has been very useful to study basic mechanisms of ocular inflammation, but is inadequate for some types of studies due to the need for active immunization in the context of strong bacterial adjuvants. We generated transgenic (Tg) mice on the B10.RIII background that express a T cell receptor (TCR) specific for IRBP161-180. Three strains of TCR Tg mice were established. Spontaneous uveitis developed in two of the three strains by 2-3 months of age. Susceptibility correlated with a higher copy number of the transgenic TCR and a higher proportion of TCR Tg T cells in the peripheral repertoire. Even in mice with uveitis, peripheral IRBP-specific CD4⁺ T cells displayed mostly a naïve phenotype. In contrast, T cells infiltrating uveitic eyes mostly showed an effector/memory phenotype, and included Th1, Th17 as well as T regulatory cells. These mice thus provide a new and distinct model of uveitis from the “classical” EAU, and may represent some types of uveitis more faithfully. Importantly, this new transgenic model of uveitis can serve as a template for therapeutic manipulations, and as a source of naïve retina-specific T cells for a variety of basic and pre-clinical studies. Several examples of such studies will be discussed.

Cite this article as:

R. Horai, W.P. Chong, R. Zhou, J. Chen, P.B. Silver, R.K. Agarwal and R.R. Caspi , Spontaneous Ocular Autoimmunity in Mice Expressing a Transgenic T Cell Receptor Specific to Retina: A Tool to Dissect Mechanisms of Uveitis, Current Molecular Medicine 2015; 15 (6) . https://dx.doi.org/10.2174/1566524015666150731095201