Role of Pathogenic T Cells in a Model of Experimental Uveoretinitis Induced by a Neoretinal Antigen

Abstract

Abstract: : Purpose: The eye is an immune privileged site which suffers from Th1 type responses that induce severe uveitis. In many human inflammatory conditions, uveitis develops secondary to an ocular infectious disease. This could result from peripheral activation, followed by ocular penetration, of Th1 cells specific for a foreign antigen expressed in the retina. To test this hypothesis, we developed a new model of experimental uveoretinitis. Methods: One month after gene transfer of influenza virus hemagglutinin (HA) into the retina of BALB/c mice, by intravitreal or subretinal injections of 2ml of recombinant adeno–associated virus, uveitis was induced by adoptive transfer of HA–transgenic T cells, followed by subcutaneous immunization with HA mixed in adjuvant. Clinical examination of animals was performed with a slit lamp biomicroscope. Infiltration of donor cells was detected by immunostaining on retina flatmounts with anti–Thy–1.1 antibody and was studied using FACS analysis. Results: Intraocular inflammation was clinically and histologically detected in all animals, between 10 to 15 days after immunization with HA. Chorioretinal infiltrates and lesions were identified after histopathological analysis. The infiltrate was composed mostly of HA–specific T–cells with a Th1 cytokine profile and macrophages. Depletion of CD25+ T–cells exacerbated the disease, suggesting their regulatory function in uveitis. Conclusions: This new animal model validates non–autoimmune mechanisms of uveitis. It will be useful to track and study pathogenic and regulatory T cells and to test new therapeutics

Keywords: pathology: experimental • inflammation • immunomodulation/immunoregulation