Purchase this article with an account.
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.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
This PDF is available to Subscribers Only