Purchase this article with an account.
Darren J. Lee, Andrew W. Taylor; Expression Of MC5r Is Required For APC Induction Of Memory Treg Cells During The Resolution Of Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2271.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
IRBP-specific memory Treg cells reside in the spleen of mice recovering from experimental autoimmune uveoretinitis (EAU). The induction of these IRBP-specific memory Treg cells is dependent on activation by nonconventional antigen presenting cells (APC) that also reside in the spleen of EAU-recovering mice. Mice recovering from EAU that have the melanocortin 5 receptor knocked out (MC5r(-/-)) do not have the IRBP-specific memory Treg cells in their spleens. Therefore, we investigated where is the dependency on the expression of MC5r in the induction of the IRBP-specific memory Treg cells during the resolution of EAU.
The C57BL/6 wild type and MC5r(-/-) mice were immunized with IRBP to induce EAU. At various times during EAU, spleen cells were collected and assayed in culture for IRBP-stimulated T cell cytokine production of IFN-γ and IL-17 by ELISA, and by bioassay for TGF-β. The spleen APC were isolated and used to stimulate cytokine production and regulatory activity in IRBP-specific T cells assayed in culture by ELISA, and flow cytometry, and in vivo by adoptive transfer into EAU mice.
The type of T cells IRBP-stimulated in the spleens of wild type EAU mice changed from Th1 and Th17 cells at the onset and height of uveitis to Treg cells at the start and during resolution of EAU. The type of IRBP-stimulated T cells in the spleen of EAU MC5r(-/-) mice were Th1 and Th17 cells throughout the course of EAU and even after resolution. The spleen APC from wild type mice recovering from EAU were able to convert the IRBP-specific Th1 cells from the EAU MC5r(-/-) mice to function as Treg cells that can suppress EAU.
During the resolution of EAU there is induction of memory Treg cells that reside in the spleen ready to suppress uveitis when activated. The induction and activation of these memory Treg cells are dependent on the presence of a nonconventional APC, which needs the expression of MC5r to function. What we have discovered is a unique consequence in the reassertion of immune privilege during the resolution of EAU that is dependent on the melanocortin pathway.
This PDF is available to Subscribers Only