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(American Journal of Pathology. 2002;161:1669-1677.)
© 2002 American Society for Investigative Pathology

Constitutive Retinal CD200 Expression Regulates Resident Microglia and Activation State of Inflammatory Cells during Experimental Autoimmune Uveoretinitis

Cathryn Broderick^*, Robert M. Hoek, John V. Forrester^*, Janet Liversidge^*, Jonathon D. Sedgwick and Andrew D. Dick

From the Department of Ophthalmology,^* University of Aberdeen, Aberdeen, United Kingdom; the Division of Ophthalmology, University of Bristol, Bristol, United Kingdom; the Department of Immunology, University Medical Centre, Utrecht, The Netherlands; and DNAX Research Incorporated, Palo Alto, California

Recent evidence supports the notion that tissue OX2 (CD200) constitutively provides down-regulatory signals to myeloid-lineage cells via CD200-receptor (CD200R). Thus, mice lacking CD200 (CD200^-/-) show increased susceptibility to and accelerated onset of tissue-specific autoimmunity. In the retina there is extensive expression of CD200 on neurons and retinal vascular endothelium. We show here that retinal microglia in CD200^-/- mice display normal morphology, but unlike microglia from wild-type CD200^+/+ mice are present in increased numbers and most significantly, express inducible nitric oxide synthase (NOS2), a macrophage activation marker. Onset and severity of uveitogenic peptide (1-20) of interphotoreceptor retinoid-binding protein-induced experimental autoimmune uveoretinitis is accelerated in CD200^-/- mice and although tissue destruction appears no greater than seen in CD200^+/+ mice, there is continued increased ganglion and photoreceptor cell apoptosis. Myeloid cell infiltrate was increased in CD200^-/- mice during experimental autoimmune uveoretinitis, although NOS2 expression was not heightened. The results indicate that the CD200:CD200R axis regulates retinal microglial activation. In CD200^-/- mice the release of suppression of tonic macrophage activation, supported by increased NOS2 expression in the CD200^-/- steady state accelerates disease onset but without any demonstration of increased target organ/tissue destruction.

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