Ocular Immunology and Inflammation, 17, 47–55, 2009 ISSN: 0927-3948 print / 1744-5078 online DOI: 10.1080/09273940802491884 Constitutive Neuronal Expression of the Immune Regulator, Programmed Death 1 (PD-1), Identified During Experimental Autoimmune Uveitis Ling Chen Departments of Ophthalmology and Molecular and Medical Pharmacology, Jules Stein Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, USA Vicky Pai and Ralph Levinson Department of Ophthalmology, Jules Stein Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, USA Arlene H. Sharpe Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA Gordon J. Freeman Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA Jonathan Braun Departments of Molecular and Medical Pharmacology and Pathology and Laboratory Medicine, and Jules Stein Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, USA Lynn K. Gordon Department of Ophthalmology, Jules Stein Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, USA; and Greater Los Angeles VA Healthcare System, Los Angeles, California, USA ABSTRACT Purpose: Programmed death-1 (PD-1) ligation downregulates active lymphocyte responses. The authors tested whether PD-1 or its ligands are expressed in the posterior segment during active intraocular inflammation. Methods: Experimental autoimmune uveitis (EAU) was induced using interphotoreceptor retinoid-binding protein (IRBP 161–180). Ocular inflammation was evaluated by histology and expression of PD-1 ligand tested by immunohistochemistry. PD-1 expression was evaluated by immunohistochemistry, RT-PCR, and Western immunoblotting. Results: Using immunohistochemistry, PD-1, but not its ligands, was constitutively expressed in retinal neurons of na¨ ıve mouse retina. Both PD-1 and its ligands were observed, as expected, in sites of active inflammation. Conclusions: PD-1 and its ligands were expressed in sites of active inflammation, in accordance with many other models of inflammatory disease. Surprisingly, PD-1, not previously described outside the immune system, was constitutively expressed in retinal neurons, raising the possibility that PD-1 signaling may be important for neuronal function in the absence of an inflammatory insult. Keywords: Brain; experimental autoimmune uveitis (EAU); immune-privilege; programmed death 1 (PD-1); retina This article is not subject to United States Copyright laws. Received 18 June 2008; accepted 10 September 2008. This work was supported by Research to Prevent Blindness (Dr. Gordon) and the Ruzic Medical Research Foundation (Dr. Braun). The authors acknowledge Paul Mischel for his helpful comments and review of brain pathology. Address correspondence to Lynn K. Gordon, MD, PhD, Jules Stein Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA. E-mail: lgordon@ucla.edu 47 Ocul Immunol Inflamm Downloaded from informahealthcare.com by CDL-UC Los Angeles on 06/09/15 For personal use only.