Regulatory T cells control NK cells in an insulitic lesion by depriving them of IL-2
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CitationSitrin, Jonathan, Aaron Ring, K. Christopher Garcia, Christophe Benoist, and Diane Mathis. 2013. “Regulatory T cells control NK cells in an insulitic lesion by depriving them of IL-2.” The Journal of Experimental Medicine 210 (6): 1153-1165. doi:10.1084/jem.20122248. http://dx.doi.org/10.1084/jem.20122248.
AbstractRegulatory T (T reg) cells control progression to autoimmune diabetes in the BDC2.5/NOD mouse model by reining in natural killer (NK) cells that infiltrate the pancreatic islets, inhibiting both their proliferation and production of diabetogenic interferon-γ. In this study, we have explored the molecular mechanisms underlying this NK–T reg cell axis, following leads from a kinetic exploration of gene expression changes early after punctual perturbation of T reg cells in BDC2.5/NOD mice. Results from gene signature analyses, quantification of STAT5 phosphorylation levels, cytokine neutralization experiments, cytokine supplementation studies, and evaluations of intracellular cytokine levels collectively argue for a scenario in which T reg cells regulate NK cell functions by controlling the bioavailability of limiting amounts of IL-2 in the islets, generated mainly by infiltrating CD4+ T cells. This scenario represents a previously unappreciated intertwining of the innate and adaptive immune systems: CD4+ T cells priming NK cells to provoke a destructive T effector cell response. Our findings highlight the need to consider potential effects on NK cells when designing therapeutic strategies based on manipulation of IL-2 levels or targets.
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