Exposure to inflammatory cytokines selectively limits GM-CSF production by induced T regulatory cells.
Bottom Line: Understanding processes that can limit this potentially deleterious effect of Treg cells in a therapeutic setting is therefore important.We show that iTreg cells can produce significant amounts of three proinflammatory cytokines (IFN-γ, GM-CSF and TNF-α) upon secondary TCR stimulation.Furthermore, we show that IL-6 and IL-27 individually, or IL-2 and TGF-β in combination, can mediate the selective loss of GM-CSF production by iTreg cells.
Affiliation: MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.Show MeSH
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Mentions: Thus far we had demonstrated that iTreg cells generated using a well characterized and widely used method would produce three proinflammatory cytokines upon secondary stimulation. We asked whether this would either diminish, or enhance, the strength of iTreg cell function using in vitro assays for suppression of naïve T cell activation. Although production of all three cytokines was again evident (data not shown), there was no apparent influence on the suppressive function of iTreg cells upon the proliferative response of naive T responder cells, stimulated by peptide-bearing APCs. Antibody neutralization of individual cytokines did not boost, or reduce, the observed suppression (Fig. 3A–C). Furthermore, IFN-γ-deficient iTreg did not have enhanced, or reduced, suppressive activity (Fig. 3D).
Affiliation: MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.