title: Inhibition of complement alternative pathway suppresses experimental autoimmune anterior uveitis by modulating T cell responses.
abstract: The objective of the current study was to delineate the pathway of complement activation that is crucial for the induction of experimental autoimmune anterior uveitis (EAAU). We studied the development of EAAU in melanin-associated antigen (MAA)-sensitized Lewis rats treated with antibody against C4 or factor B. Control animals received isotype IgG control. Antibody against C4 had no effect on EAAU, and all of the animals developed EAAU similar to those injected with control IgG. In contrast, EAAU was completely inhibited in all MAA-sensitized Lewis rats injected with factor B antibody. Treatment with anti-factor B antibody resulted in suppression of ocular complement activation. Adoptive transfer of T lymphocytes harvested from draining lymph nodes of donor animals treated with anti-factor B did not transfer EAAU to naïve syngenic rats. Anti-factor B antibody inhibited the ability of MAA-specific CD4(+) T cells to proliferate (in vitro) in response to MAA in a dose-dependent manner. Level of TNF-α and IFN-γ decreased in the presence of anti-factor B. Collectively, our results provide the novel finding that complement activation via the alternative pathway contributes to intraocular inflammation in EAAU, and anti-factor B-mediated inhibition of EAAU is due to diminished antigen-specific CD4(+) T cell responses to MAA. Our findings explain the interactions between the complement system and T cells that are critical for the induction of EAAU and may lead to the development of therapy for idiopathic anterior uveitis based on selective blockade of the alternative pathway.
authors.affiliation: From the Department of Ophthalmology, Jones Eye Institute, Pat and Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205.
authors.forename: Balasubramanian
authors.initials: B
authors.lastname: Manickam
authors.affiliation: From the Department of Ophthalmology, Jones Eye Institute, Pat and Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205.
authors.forename: Purushottam
authors.initials: P
authors.lastname: Jha
authors.affiliation: From the Department of Ophthalmology, Jones Eye Institute, Pat and Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205.
authors.forename: Bharati
authors.initials: B
authors.lastname: Matta
authors.affiliation: From the Department of Ophthalmology, Jones Eye Institute, Pat and Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: From the Department of Ophthalmology, Jones Eye Institute, Pat and Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205.
authors.forename: Puran S
authors.initials: PS
authors.lastname: Bora
authors.affiliation: From the Department of Ophthalmology, Jones Eye Institute, Pat and Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205. Electronic address: nbora@uams.edu.
authors.forename: Nalini S
authors.initials: NS
authors.lastname: Bora
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003181:Complement C4 / Q000276:immunology*; D011415:Complement Factor B / Q000276:immunology*; D003170:Complement Pathway, Alternative / Q000187:drug effects / Q000276:immunology*; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D008297:Male; D008543:Melanins / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D003181:Complement C4; D007074:Immunoglobulin G; D008543:Melanins; D011415:Complement Factor B