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B.P. Vistica, J. Chen, H. Takase, D.–.I. Ham, E.F. Wawrousek, C.E. Egwuagu, C.–.C. Chan, I. Gery; Different Models of Ocular Inflammation: Variability in the Populations of Infiltrating Cells . Invest. Ophthalmol. Vis. Sci. 2005;46(13):969.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Conventional models of immune–mediated inflammation, such as experimental autoimmune uveitis (EAU), are triggered by TCR engagement on T–cells, followed by the activation of these cells and their release of inflammation–mediating cytokines. We have shown, however, that inflammatory changes develop in mouse eyes in which interleukin (IL)–1 or IL–7 are expressed transgenically. Here, we compared the histopathological changes and the populations of infiltrating cells in eyes developing EAU, or inflammation due to expression of cytokines. Methods: EAU was induced in B10.RIII mice by immunization with IRBP peptide 161–180, whereas IL–1, IL–7 and interferon–gamma (IFN–γ) transgenic (Tg) mice were generated in FVB/N mice, by placing the cytokine genes under control of the alpha–A crystallin promoter. Hematoxylin & eosin staining on the methacrylate embedded ocular sections was used for the histological examination, while conventional flow cytometric methods were used for identification of the infiltrating cells, following collagenase digestion of the affected eyes. Results: Panuveitic changes were seen in mice with EAU and in the IL–1 and IL–7 Tg mice. In contrast, the eyes of the IFN–γ Tg mice illustrated total retinal detachment, but no significant inflammation. A feature unique to the IL–1 and IL–7 Tg mice was the heavy accumulation of inflamatory cells in the limbus, consisting mostly of lymphocytes in IL–7 Tg mice, or a mixed population in the IL–1 Tg animals. Flow cytometric analysis of the infiltrating cells revealed that CD3+ cells comprised 55–63% in all three groups, with the majority of these cells being CD4 cells in all mice, but with more CD8 in EAU eyes (32%) than in the IL–1 or IL–7 Tg mice (12% and 7% respectively). Very few B–cells (CD19) were found in eyes with EAU, while IL–1 Tg eyes had 36% and IL–7 had 12% of these cells. On the other hand, EAU eyes had 34% macrophages (F4/80) vs essentially no such cells in the eyes of Tg mice. Conclusions: The panuveitis induced by local expression of IL–1 or IL–7 differs from those changes elicited by TCR engagement (EAU) in its composition of infiltrating cells as well as by its typical histological features.
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