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N. Golestaneh, C.-R. Yu, C. E. Egwuagu; IL-23 Confers Survival to Th17 Cells by Inducing Endogenous Production of IL-2. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2639.
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We previously showed that Th17 cells are present in blood of healthy humans and their levels are several folds higher in uveitis or scleritis patients. Using the EAU model we provided evidence implicating Th17 cells in the etiology of uveitis. In this study, we have investigated mechanisms that allow Th17 cells to survive and persist in peripheral tissues.
Naïve CD4 T cells were isolated from lymph nodes and spleens of C57Bl6 mice and purified on anti-CD4 antibody conjugated beads. The cells were polarized toward Th1 or Th17 cells using requisite cytokines/antibodies and cells were cultured for 24h, 48h, 72h or 96h. The 96h-cultures were expanded for 4 days in medium containing IL-23 and/or IL-2 and intracellular secretion of IL-2, IL-17, IL-10 or IFN-γ was detected/quantified by FACS or ELISA. Cytokine mRNA transcripts were detected and quantified by real-time PCR.
We show here that Th1 cells produce high levels of IL-2 after 48h of polarization and this level decreased significantly at 96h, suggesting that secretion of IL-2 by Th1 cell is transient. Conversely, production of IL-2 by Th17 cells increased with time and subsequent diminution of IL-2-secreting cells was not observed. Furthermore, whereas IL-2 induces substantial expansion of Th1 cells, it has marginal effects on Th17 cells. In fact, addition of exogenous IL-2 to the culture during the expansion phase induced a decline in the number of Th17 cells, as well as, in IL-2-secreting Th17 cells. In contrast, IL-23 induces an increase in Th17 cells and the expansion coincided with marked increase in numbers of IL-2-secreting Th17 cells.
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