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B. P. Vistica, G. Shi, M. Ramaswamy, C. Tan, E. F. Wawrousek, R. M. Siegel, I. Gery; Th17 Cells, but Not Th1, Mediate Sustained Autoimmune Inflammation in the Eye by Their Relative Resistance to Restimulation-Induced Cell Death (RICD). Invest. Ophthalmol. Vis. Sci. 2009;50(13):2633.
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We previously showed that polarized lines of both Th1 and Th17 cells, specific against hen egg lysozyme (HEL), induce ocular inflammation in recipient mice expressing HEL in their eyes (Cox et al, J. Immunol., 2008, 180:7414). Here, we compared the two Th lineages for several parameters related to induction of ocular inflammation in recipient mice.
Rate of division following transfer was determined by the CFSE dilution method. The kinetics of inflammation development and severity of disease were determined by histological analysis at different time points. Fas expression was measured by flow cytometry. Sensitivity to RICD was measured by the anti CD3 antibody assay.Transcript levels of FasL were determined by real-time PCR.
Polarized Th1 divided in recipient mice considerably faster than Th17, as measured by CFSE dilution. Th1 also invaded recipient eyes earlier than Th17: onset of the inflammatory process was day 3 for Th1 and day 4 for Th17. After reaching the severity peak, the inflammatory process in Th1 recipient eyes receded rapidly, but was sustained in Th17 recipient eyes throughout the 15 days testing period. Importantly, Th1 and Th17 differed profoundly in the kinetics of their presence in the inflamed eye: Th17 remained the majority among eye infiltrating cells and their actual number even increased slightly during the observation period, while Th1 cell number declined following their peak around day 5 and their proportion among infiltrating cells declined rapidly. Th17 were more resistant to RICD, a major pathway whereby restimulated Th are eliminated. This resistance to apoptosis was due at least in part to a compromised Fas-induced apoptosis pathway in Th17 relative to Th1 cells, despite normal expression of Fas. Moreover, Th1 cells expressed a higher level of FasL than Th17 cells and Th1 recipient eyes had a higher expression level of FasL than Th17 recipient eyes.
Th1- and Th17- mediated inflammatory processes differ in their kinetics, due in part to the relative resistance of Th17 to RICD.
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