March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Identification of a MC5r+ Gr-1low F4/80+ CD11b+ APC Associated with EAU Recovery
Author Affiliations & Notes
  • Darren J. Lee
    Ophthalmology, Boston University School of Med, Boston, Massachusetts
  • Andrew W. Taylor
    Ophthalmology, Boston University School of Med, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Darren J. Lee, None; Andrew W. Taylor, None
  • Footnotes
    Support  NIH Grant EY010752, Massachusetts Lions Eye Research Foundation
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 6309. doi:
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      Darren J. Lee, Andrew W. Taylor; Identification of a MC5r+ Gr-1low F4/80+ CD11b+ APC Associated with EAU Recovery. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6309.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Mice that have recovered from experimental autoimmune uveoretinitis (EAU) have developed IRBP-specific regulatory immunity in the spleen. This post-EAU regulatory immunity is mediated by tolerogenic APC, and requires melanocortin 5 receptor (MC5r) expression. Also, treating EAU mice with an adenosine 2A receptor (A2Ar) agonist promotes induction of regulatory immunity. Therefore, we further characterized the MC5r-dependent tolerogenic APC, and determined the role of A2Ar expression in mediating the presence of tolerogenic APC in the post-EAU spleen.

Methods: : C57BL/6 (WT) and A2Ar(-/-) mice were immunized with interphotoreceptor retinoid binding protein (IRBP) in adjuvant to induce EAU. At resolution of EAU, spleen APC were collected and stained for CD11b, Gr-1, and F4/80. Flow cytometry analysis, and sorting was done. The sorted cells were pulsed with IRBP and used as APC to stimulate IFN-γ production by syngeneic IRBP-specific Th1 cells. Primary peritoneal macrophages from WT and MC5r(-/-) mice were stained for CD11b, Gr-1, and F4/80, and analyzed by flow cytometry.

Results: : The spleen had Gr-1low and Gr-1high F4/80+ CD11b+ cells with a defined increase in Gr-1low cells and corresponding decrease of Gr-1high cells in the post-EAU WT spleen. The T cells stimulated by the sorted Gr-1low F4/80+ CD11b+ APC were greatly diminished in IFN-γ. While the course of EAU was no different in comparison to EAU WT mice, the post-EAU A2Ar(-/-) mice had no regulatory immunity in the spleen. There was no change in the percentage of spleen Gr-1low F4/80+ CD11b+ cells in the post-EAU A2Ar(-/-) mice compared to post-EAU WT mice; however, there was an increase in Gr-1high F4/80+ CD11b+ cells. Primary macrophages from MC5r(-/-) mice were highly deficient in Gr-1+ and F4/80+ CD11b+.

Conclusions: : The development of post-EAU regulatory immunity in the spleen is associated with the expansion of Gr-1low F4/80+ CD11b+ APC in the spleen that suppresses effector T cell activation. The APC presence, and possibly development, is dependent on expressing MC5r, but not on A2Ar. Therefore, the post-EAU regulatory immunity is mediated by a MC5r+ Gr-1low F4/80+ CD11b+ APC, and the A2Ar mediated suppression must be through other cells involved in immune regulation such as Treg cells.

Keywords: uveitis-clinical/animal model • autoimmune disease • immunomodulation/immunoregulation 
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