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R. E. Cone, C. Broughton, R. Louisant, J. O'Rourke, R. B. Clark; Regulation of Autoimmunity by Anterior Chamber-Induced Regulatory T Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2505. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Although the injection of autoantigen into the anterior chamber can mitigate autoimmune disease, most investigations on the regulation of autoimmunity by Anterior Chamber-Associated Immune Deviation (ACAID) do not discriminate between the regulation of the afferent or efferent stages of autoimmunity. Here we investigated the hypothesis that the injection of myelin antigens into the anterior chamber induces T cells that specifically regulate Experimental Allergic Encephalomyleitis (EAE) induced by immunization or activated, encephalitogenic T cells.
EAE was induced by the iv injection of the encephalitogenic,bovine myelin basic protein (BMBP)-specific SJL CD4+ T cell clone MM-4 into naïve SJL mice or by the sc injection of myelin oligodendrocyte glycoprotein (MOG) peptide, Complete Freund’s Adjuvant and pertussis into C57BL/6 mice. The DTH response to BMBP or MOG peptide was induced by the id injection of BMBP or MOG peptide into a footpad of BMBP or MOG peptide-immunized mice. The suppression of the cell-mediated immune response to BMBP or MOG peptide and splenic regulatory T cells (AC-SPL cells) was/were induced by the injection of BMBP or MOG peptide into the AC. The production of AC-SPL cells was inhibited by ablation of the sympathetic nervous system by the injection of 6-hyroxydopamine (6-OHDA).
EAE induced by clone MM-4 or MOG peptide was prevented or reduced markedly in mice receiving a prior intracameral injection of BMBP or MOG peptide respectively. EAE was enhanced in 6-OHDA-treated mice. AC-SPL cells from mice receiving intracameral BMBP or MOG specifically suppressed the DTH reaction to BMBP or MOG respectively in a local transfer of suppression. EAE was not induced in mice receiving MM-4 and AC-SPL cells from donors that received an injection of BMBP into the AC. Alternatively, EAE was less severe and these mice had a longer life span than mice injected with MM-4 only. CD4+ AC-SPL cells suppressed BMBP-induced proliferation of MM-4 in vitro but did not suppress BMBP-induced production of interferon-γ. CD8+ AC-SPL cells suppressed BMBP-induced IFN-γ production in vitro.
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