A transgenic mouse model for autoimmune uveitis

Purpose. This study was designed to produce a mouse model in which the antigenspecific. CD4' T cell responsible for mediating autoimmunity could be physically tracked in vivo, and easily manipulated in vitro for functional analysis. We have previously established that an adoptive transfer system using T cells from the OVA specific, DO11.10 TCR transgenic mouse provides an excellent system for the study of the T cell response to exogenously administered OVA. If OVA could be expressed as a sell' antigen, then this system would be ideally suited for the study of the mechanisms of autoreactivity and tolerance. Methods. Transgenic mice were produced using a rhodopsin promoter/ovalbumin cDNA construct. Transgene expression was determined by ELISA of extracted eye fluid. Eyes were examined by slit lamp exam and standard histological techniques. Results. Four founder lines of transgenic mice were produced. All lines expressed approximately 1 ng of OVA/eye as assessed by ELISA of ocular tluid indicating that sufficient OVA is secreted from the retina to serve as a useful self neoantigen. None of the mice exhibited ocular abnormalities or inflammation indicating they will be good models for the study of autoimmunity. The BALB/c-Rho/OVA transgenic mice were crossed to the DO1L10 TCR transgenic mice and double transgenic mice have been obtained. These mice will be characterized for the presence of inflammatory infiltrate, and the possible tolerizing effect of ocular OVA on OVA specific T cells will be monitored by staining with the clonotypic mAb, KJ1-26, and by functional analysis. Conclusions These mice should serve as an excellent model for studying the mechanisms of T cell reactivity and tolerance to an ocular self antisen.