Abrogation of Anti-Retinal Autoimmunity in IL-10 Transgenic Mice Due to Reduced T Cell Priming and Inhibition of Disease Effector Mechanisms

• Published in: The Journal of immunology (1950) 2008-04, Vol.180 (8), p.5423-5429
• Main Authors: Agarwal, Rajeev K, Horai, Reiko, Viley, Angelia M, Silver, Phyllis B, Grajewski, Rafael S, Bo Su, Shao, Yazdani, Arrash T, Zhu, Wei, Kronenberg, Mitchell, Murray, Peter J, Rutschman, Robert L, Chan, Chi-Chao, Caspi, Rachel R
• Format: Article
• Language: English
• Subjects: Animals; Antigen Presentation; Autoimmune Diseases - immunology; Autoimmunity; Disease Models, Animal; Eye Proteins - immunology; Interleukin-10 - genetics; Interleukin-10 - immunology; Interleukin-10 - metabolism; Lymphocyte Activation; Macrophages - immunology; Macrophages - metabolism; Major Histocompatibility Complex - genetics; Mice; Mice, Inbred C57BL; Mice, Transgenic; Retina - immunology; Retinol-Binding Proteins - immunology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Uveitis - immunology; Uveitis - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.180.8.5423

Experimental autoimmune uveitis (EAU) induced by immunization of animals with retinal Ags is a model for human uveitis. The immunosuppressive cytokine IL-10 regulates EAU susceptibility and may be a factor in genetic resistance to EAU. To further elucidate the regulatory role of endogenous IL-10 in the mouse model of EAU, we examined transgenic (Tg) mice expressing IL-10 either in activated T cells (inducible) or in macrophages (constitutive). These IL-10-Tg mice and non-Tg wild-type controls were immunized with a uveitogenic regimen of the retinal Ag interphotoreceptor retinoid-binding protein. Constitutive expression of IL-10 in macrophages abrogated disease and reduced Ag-specific immunological responses. These mice had detectable levels of IL-10 in sera and in ocular extracts. In contrast, expression of IL-10 in activated T cells only partially protected from EAU and marginally reduced Ag-specific responses. All IL-10-Tg lines showed suppression of Ag-specific effector cytokines. APC from Tg mice constitutively expressing IL-10 in macrophages exhibited decreased ability to prime naive T cells, however, Ag presentation to already primed T cells was not compromised. Importantly, IL-10-Tg mice that received interphotoreceptor retinoid-binding protein-specific uveitogenic T cells from wild-type donors were protected from EAU. We suggest that constitutively produced endogenous IL-10 ameliorates the development of EAU by suppressing de novo priming of Ag-specific T cells and inhibiting the recruitment and/or function of inflammatory leukocytes, rather than by inhibiting local Ag presentation within the eye.