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Amy Ward, Oliver Hugh Bell, Louis Scott, David Copland, Andrew D Dick, Lindsay B Nicholson; Upregulation of CX3CR1 on CD4+ T cells during Experimental Autoimmune Uveoretinitis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):784.
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© ARVO (1962-2015); The Authors (2016-present)
Non-infectious uveitis is a T cell mediated intraocular inflammatory disease often leading to visual impairment. Experimental autoimmune uveitis (EAU) is an animal model that shares many features of the human disease. It can be induced by transferring autoantigen specific lymphocytes. CX3CR1 is the receptor for CX3CL1 and its expression has been associated with persistent inflammation in the lung and skin. The aim of this study is to quantify intra-ocular CX3CR1 expression on CD4+ T cells in EAU.
Autoantigen specific lymphocytes were obtained from retinal antigen immunized CX3CR1+/GFP reporter mice and transferred to naïve recipients. Following transfer of 1-2x106 activated cells clinical disease was assessed by high resolution imaging and flow cytometric analysis over three weeks disease course duration.
At day 2, CX3CR1 was expressed on both endogenous and transferred CD4+ T cell population in the retina. The frequency of GFP expression is low immediately following transfer (9%) but increases as clinical disease develops. At day 7, 21% of transferred cells express GFP, rising to 50% at day 14. Surface staining with anti-CX3CR1 as well as GFP expression was carried out to compare the frequency of total CX3CR1 expression in the transferred and endogenous populations. At all time points, the frequency of CX3CR1 expression in the retina was greater in transferred cell populations. Even out to day 21 disease, there remained an over-representation of CX3CR1+ CD4+ on transferred (Mean= 0.42, SD= 0.3) versus endogenous (Mean= 0.14, SD= 0.11) T cells.
These studies suggest within the eye, a subset of CD4 cells have a tissue specific phenotype defined by the expression of CX3CR1, which promotes their survival and retention at the site of persistent inflammation. Long-lived disease-causing cells are therefore a candidate for targeted immune-intervention.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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