The in vivo and in vitro induction of anterior chamber associated immune deviation to myelin antigens in C57BL/6 mice

Introduction of antigens into the anterior chamber (AC) of the eye generates a specific systemic form of tolerance that is termed AC-associated immune deviation (ACAID). Experimental autoimmune encephalomyelitis (EAE) is an animal model of the human CNS demyelinating diseases, including multiple sclerosis (MS) and acute disseminated encephalomyelitis. We investigated whether the encephalitogenic antigens myelin oligodendrocyte glycoprotein (MOG(35-55)) or myelin basic protein (MBP) induce ACAID in the EAE-prone C57BL/6 mice. We hypothesized that injection of MOG(35-55)/MBP induces antigen-specific tolerance whether via the AC route, the adoptive transfer of in vitro-generated MOG(35-55)-specific/MBP-specific ACAID antigen presenting cells (APCs), or the adoptive transfer of MOG(35-55)-specific/MBP-specific ACAID T regulatory cells (Tregs). ACAID is characterized by the specific impairment of delayed-type hypersensitivity (DTH) responses. Thus, DTH assays were used to test for ACAID following the AC injection of MOG(35-55)/MBP, or the intravenous injection of MOG(35-55)-specific/MBP-specific ACAID APCs. The functional local adoptive transfer (LAT) assays were used to examine the putative regulatory functions of in vitro generated MOG(35-55)-specific/MBP-specific Tregs. This report is the first to demonstrate the in vivo and in vitro induction of MOG(35-55)-specific/MBP-specific ACAID-mediated tolerance in C57BL/6 mice. These findings highlight the need for novel immunotherapeutic strategies for MS and optic neuritis. (C) 2014 Elsevier Inc. All rights reserved.