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R. Horai, R. K. Agarwal, A. M. Viley, P. B. Silver, A. Yazdani, M. Kronenberg, P. J. Murray, R. L. Rutschman, C. C. Chan, R. R. Caspi; Abrogation of Anti-Retinal Autoimmunity in Transgenic Mice Overexpressing IL-10 in a Cell-Specific Fashion. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1993. doi: https://doi.org/.
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Experimental autoimmune uveitis (EAU) induced by immunization of animals with retinal antigens is a model for human uveitis. IL-10 regulates EAU susceptibility and may be a factor in genetic resistance to EAU. To further elucidate the regulatory role of IL-10 in the mouse model of EAU, we examined the effects of transgenic IL-10 expressed under control of cell-specific promoters.
We used three lines of IL-10 transgenic (Tg) mice that overexpress IL-10 either in activated T cells (inducible, two lines) or in macrophages (constitutive). To induce EAU, mice were immunized with interphotoreceptor retinoid-binding protein (IRBP). IRBP-specific responses were assessed by histopathology, delayed-type hypersensitivity, lymphocyte proliferation and cytokine secretion, or by adoptive transfer of uveitogenic effector T cells from wild type donors.
Constitutive expression of IL-10 in macrophages abrogated disease and reduced Ag-specific immunological responses. These mice had detectable levels of IL-10 in serum and in ocular extracts. In contrast, inducible 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. Ag-presenting cells from Tg mice constitutively expressing IL-10 in macrophages exhibited decreased ability to prime naïve T cells, however, Ag presentation to already primed T cells was not compromised. Importantly, IL-10 Tg mice that received IRBP-specific uveitogenic T cells from wild type donors were protected from EAU.
Constitutively produced endogenous IL-10 appears to ameliorate development of EAU by suppressing the priming of Ag-specific T cells as well as the recruitment and function of inflammatory leukocytes, rather than by inhibiting local Ag presentation within the eye.*R. Horai and R.K. Agarwal contributed equally to the work.
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