Ocular regulatory T cells distinguish monophasic from recurrent autoimmune uveitis.

PURPOSE To determine whether CD4(+)CD25(+) T-regulatory cells (Tregs) from the eyes of rats with recurrent (r) experimental autoimmune uveitis (EAU) were less efficient in suppressing intraocular inflammation than those from rats with monophasic (m) disease (m-EAU). METHODS m-EAU and r-EAU were induced in Lewis rats 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 were determined. Aqueous humor (AqH) from m-EAU and r-EAU was collected and studied for its ability to enhance ocular Treg function. RESULTS The authors found that the number of ocular CD4(+)CD25(+) (Tregs) increased in the eye during resolution of the first acute attack of intraocular inflammation in m-EAU and r-EAU. However, the suppressor function of these cells was 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 to a monophasic disease. CONCLUSIONS This study demonstrated that although a number of mechanisms may contribute to the recurrence of intraocular inflammation, dysregulation and malfunction of Tregs in the eye are important factors in disease recurrence.