The Role ofM. lepraeHsp65 Protein and Peptides in the Pathogenesis of Uveitis

Abstract

Experimental autoimmune uveitis (EAU) is a well established model for immune-mediated organ-specific disease. Our group has recently shown that theM. lepraeHsp65 aggravated the uveitis in mice; in the present study, we evaluated the action ofM. leprae  K409Amutant protein and the synthetic peptides Leader pep andK409Apep (covering amino acids residues 352–371 of WT andK409Aproteins ofM. lepraeHsp65, resp.) on the pathogenesis of EAU. Mice received the 161–180 IRBP peptide andB. pertussistoxin followed by the intraperitoneal inoculation ofK409Aprotein or the Leader pep orK409Apep. The Leader pep aggravated the disease, but mice receiving theK409Apep did not develop the disease and presented an increase in IL-10 levels by spleen cells and a decrease in the percentage of CD4+ IFN-γ+ T cells. Moreover, animals receiving the Leader pep presented the highest scores of the disease associated with increase percentage of CD4+ IFN-γ+ T cells. These results would contribute to understanding of the pathogenesis of EAU and support the concept that immune responses to Hsp are of potential importance in exacerbating, perpetuating, or even controlling organ-restricted autoimmune diseases, and it is discussed the irreversibility of autoimmune syndromes.