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Toshikatsu Kaburaki, Xiangyuan Jin, Masateru Uchiyama, Mitsuko Takamoto, Hisae Nakahara, Hidetoshi Kawashima, Shiro Amano, Masanori Niimi; Intratracheal Administration of Interphotoreceptor Retinoid-Binding Protein Peptide Suppress Murine Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2525.
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© ARVO (1962-2015); The Authors (2016-present)
Mucosal administration of autoantigens results in the development of a state of peripheral immunological tolerance. Previous study demonstrated that intranasal administration of retinal antigens induced transient T cell activation and apoptosis within drainage lymph nodes but not spleen in murine experimental autoimmune uveitis (EAU) model. In this study, we examined the effects of intratracheal administraton of retinal antigens in murine EAU and clarified the mechanisms of the suppression of uveitis.
Murine EAU (C57BL6) was induced with subcutaneous injection of human interphotoreceptor retinoid-binding protein (IRBP) peptide mixed with complete Freund’s adjuvant. In IRBP-treated group (I-Group), 100µg of IRBP peptide was administrated intratracheally 7 days before immunization, whereas in control group (C-group), 100µg of saline was administrated. Clinical and histopathological scoring of EAU, cytokine production, T cell proliferation assay and numbers of CD4+CD25+Fox-p3+ regulatory T (Treg) cells in regional lymph nodes and spleen were examined.
The average histopathological EAU score was 2.5±1.5 in C-group and 1.1±1.2 in I-group at 21 days after immunization (p<0.01, Student’s unpaired t-test), respectively. Interferon-γ and IL-12 production in regional lymph nodes cells and splenocytes were significantly suppressed in I-group compared to those in C-group (p<0.05). Antigen-specific T cell proliferation of regional lymph nodes cells and splenocytes were also significantly suppressed in I-group compared to those in C-group (p<0.05). The percentages of Treg cells in the whole regional lymph nodes cells and splenocytes were significantly increased in I-group (3.87±0.20% and 3.90±0.76%) compared to those in C-group (2.93±0.14% and 2.67±0.67%, p<0.01).
Intratracheal administration of IRBP peptide has an inhibitory effect on murine EAU, probably through the increase of Treg cells in regional lymph nodes and spleen and the decrease of antigen-specific T cells.
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