May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Abrogation of Anti-Retinal Autoimmunity in Transgenic Mice Overexpressing IL-10 in a Cell-Specific Fashion
Author Affiliations & Notes
  • R. Horai
    Laboratory of Immunology, NEI, NIH, Bethesda, Maryland
  • R. K. Agarwal
    Laboratory of Immunology, NEI, NIH, Bethesda, Maryland
  • A. M. Viley
    Laboratory of Immunology, NEI, NIH, Bethesda, Maryland
  • P. B. Silver
    Laboratory of Immunology, NEI, NIH, Bethesda, Maryland
  • A. Yazdani
    Laboratory of Immunology, NEI, NIH, Bethesda, Maryland
  • M. Kronenberg
    LIAI, La Jolla, California
  • P. J. Murray
    Dept. of Infectious Diseases, St. Jude Children's Hosp., Memphis, Tennessee
  • R. L. Rutschman
    Dept. of Infectious Diseases, St. Jude Children's Hosp., Memphis, Tennessee
  • C. C. Chan
    Laboratory of Immunology, NEI, NIH, Bethesda, Maryland
  • R. R. Caspi
    Laboratory of Immunology, NEI, NIH, Bethesda, Maryland
  • Footnotes
    Commercial Relationships  R. Horai, None; R.K. Agarwal, None; A.M. Viley, None; P.B. Silver, None; A. Yazdani, None; M. Kronenberg, None; P.J. Murray, None; R.L. Rutschman, None; C.C. Chan, None; R.R. Caspi, None.
  • Footnotes
    Support  NIH Intramural Funding
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1993. doi:https://doi.org/
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: uveitis-clinical/animal model • cytokines/chemokines • transgenics/knock-outs 
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