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Y. Bian, Y. Ke, D. Sun, G. Jiang, H. J. Kaplan, H. Shao; Reduced Inhibitory Function of Ocular Regulatory T Cells in Recurrent Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2516. doi: https://doi.org/.
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To determine whether CD4+CD25+ T regulatory cells (Tregs) from the eyes of rats with recurrent EAU (r-EAU) were less efficient in suppressing intraocular inflammation than those from rats with monophasic disease (m-EAU).
m-EAU and r-EAU were induced in Lewis rats either by immunization with R16 or by adoptive transfer of R16-specific T cells, respectively. Ocular CD4+CD25+ Tregs were separated from CD4+ CD25- T effector cells and the inhibitory functions of Tregs determined. Aqueous humor (AqH) from m-EAU and r-EAU were collected and studied for their ability to enhance ocular Treg function.
We found that the number of ocular CD4+CD25+ (Tregs) increased in the eye during resolution of the first acute attack of intraocular inflammation in both m-EAU and r-EAU. However, the suppressor function of these cells was much weaker in r-EAU. The suppressor function of ocular Tregs in r-EAU was enhanced by incubation with AqH from animals recovering from m-EAU. Moreover, the weaker suppressor function of ocular Tregs in r-EAU correlated with low or undetectable levels of IL-10 in the AqH, and was reversed by the addition of IL-10 to the AqH. Finally, the transfer of ocular Tregs from animals with m-EAU converted r-EAU into a monophasic disease.
Our study demonstrated that although a number of mechanisms may contribute to the recurrence of intraocular inflammation, dysregulation and malfunction of Tregs in the eye is an important factor in disease recurrence.
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