Ke Yan, Jiang Guomin, Sun Deming, Kaplan Henry J, Shao Hui
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, Kentucky, USA.
Invest Ophthalmol Vis Sci. 2008 Sep;49(9):3999-4007. doi: 10.1167/iovs.07-1468. Epub 2008 May 16.
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).
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.
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.
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.
确定复发性（r）实验性自身免疫性葡萄膜炎（EAU）大鼠眼中的CD4(+)CD25(+)调节性T细胞（Tregs）在抑制眼内炎症方面是否比单相（m）疾病（m-EAU）大鼠的Tregs效率更低。
分别通过用R16免疫或通过过继转移R16特异性T细胞在Lewis大鼠中诱导m-EAU和r-EAU。从CD4(+) CD25(-)效应T细胞中分离出眼内CD4(+)CD25(+) Tregs，并测定Tregs的抑制功能。收集m-EAU和r-EAU的房水（AqH），并研究其增强眼内Treg功能的能力。
作者发现，在m-EAU和r-EAU的首次急性眼内炎症发作消退期间，眼内CD4(+)CD25(+)（Tregs）数量增加。然而，这些细胞在r-EAU中的抑制功能较弱。r-EAU中眼内Tregs的抑制功能通过与从m-EAU恢复的动物的AqH孵育而增强。此外，r-EAU中眼内Tregs较弱的抑制功能与AqH中低水平或无法检测到的IL-10相关，并且通过向AqH中添加IL-10而逆转。最后，将m-EAU动物的眼内Tregs转移可将r-EAU转变为单相疾病。
本研究表明，虽然多种机制可能导致眼内炎症复发，但眼内Tregs的失调和功能障碍是疾病复发的重要因素。
