Analysis of retinal cellular infiltrate in experimental autoimmune uveoretinitis reveals multiple regulatory cell populations

被引:140
作者
Kerr, Emma C. [1 ]
Raveney, Ben J. E. [1 ]
Copland, David A. [2 ]
Dick, Andrew D. [1 ,2 ]
Nicholson, Lindsay B. [1 ,2 ]
机构
[1] Univ Bristol, Sch Med Sci, Dept Cellular & Mol Med, Bristol BS8 1TD, Avon, England
[2] Univ Bristol, Clin Sci S Bristol, Acad Unit Ophthalmol, Bristol Eye Hosp, Bristol BS1 2LX, Avon, England
关键词
Experimental autoimmune uveoretinitis; Myeloid-derived suppressor cells; Interleukin-17; T regulatory cells;
D O I
10.1016/j.jaut.2008.08.006
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Experimental autoimmune uveoretinitis (EAU) is an animal model for human intraocular inflammatory disease. EAU is induced in B10.RIII mice by immunization with RBP-3 161-180 peptide and intraperitoneal pertussis toxin and is mediated by CD4(+) T cells that generate a clinically monophasic disease peaking approximately 2 weeks post-immunization. Collagenase digestion of retinal tissue allowed the quantification and characterization of leukocytes in the inflamed retina during disease progression. Using this method we identified three stages of disease. Initially there is a prodromal phase where we found significant changes in the number of leukocytes in the eye as early as 5 days post-immunization. This effect was, in part, non-antigen specific as a small increase in retinal leukocytes was also observed following immunization with OVA peptide. Following the prodrome there is a primary peak of infiltration including both CD4(+) T cells and CD11b(+) cells. This coincides with an early influx of neutrophils and is associated with a peak in IL-17-producing T cells. The neutrophils in the eye are CD11b(+) and Gr1(+) but can be distinguished from other myeloid cells by their high expression of Ly6G. The remaining CD11b(+)Gr1(+) cells can suppress proliferation and are analogous to myeloid derived suppressor cells which are found in tumors. The inflamed eye also contains a considerable proportion of FoxP3(+) regulatory cells. Following peak disease, the retina does not return to its pre-disease phenotype. Instead, fluctuations in infiltrating leukocyte numbers and changes to their relative composition continue, indicating that clinical recovery does not equate to the restoration of a normal retinal leukocyte population. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:354 / 361
页数:8
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