title: The in vivo and in vitro induction of anterior chamber associated immune deviation to myelin antigens in C57BL/6 mice.
abstract: 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 (MOG35-55) or myelin basic protein (MBP) induce ACAID in the EAE-prone C57BL/6 mice. We hypothesized that injection of MOG35-55/MBP induces antigen-specific tolerance whether via the AC route, the adoptive transfer of in vitro-generated MOG35-55-specific/MBP-specific ACAID antigen presenting cells (APCs), or the adoptive transfer of MOG35-55-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 MOG35-55/MBP, or the intravenous injection of MOG35-55-specific/MBP-specific ACAID APCs. The functional local adoptive transfer (LAT) assays were used to examine the putative regulatory functions of in vitro generated MOG35-55-specific/MBP-specific Tregs. This report is the first to demonstrate the in vivo and in vitro induction of MOG35-55-specific/MBP-specific ACAID-mediated tolerance in C57BL/6 mice. These findings highlight the need for novel immunotherapeutic strategies for MS and optic neuritis.
authors: Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA.
authors: Shukkur M
authors: SM
authors: Farooq
authors: Department of Microbiology & Immunology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt; Department of Pediatrics, Eastern Virginia Medical School, Norfolk, VA, USA; Department of Pharmacy Practice, School of Pharmacy, Hampton University, Hampton, VA, USA.
authors: Walid F
authors: WF
authors: Elkhatib
authors: Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA; Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address: hossamking@mailcity.com.
authors: Hossam M
authors: HM
authors: Ashour
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects / Q000276:immunology*; D004195:Disease Models, Animal; D007108:Immune Tolerance / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology*; D009186:Myelin Sheath / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000008:administration & dosage / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
chemical_list: D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein
keywords: ACAID; CD8(+) Tregs; DTH assay; EAE; Immune privilege; LAT assay; MBP; MOG; Multiple sclerosis; Peripheral tolerance; Regulatory T cells