An essential role for the IL-2 receptor in Treg cell function

Regulatory T (Treg) cells, expressing abundant amounts of the IL-2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature implied a key role for a simple network based on IL-2 consumption by Treg cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the Treg lineage specification factor Foxp3, confounding experimental efforts to understand the role of IL-2R expression and signaling in Treg suppressor function. Using genetic gain and loss of function approaches, we demonstrate that IL-2 capture is dispensable for control of CD4+ T cells, but is important for limiting CD8+ T cell activation, and that IL-2R dependent STAT5 transcription factor activation plays an essential role in Treg suppressor function separable from T cell receptor signaling. Overall design: Gene expression profiles in Treg cells with or without an expression of an active form of STAT5 were compared by RNA sequencing. Male 8-wk-old Foxp3Cre-ERT2Rosa26Stat5bCA (STAT5b-CA) and Foxp3Cre-ERT2 (control) mice, nine mice for each experimental group, received a single dose (4 mg) of tamoxifen by oral gavage 4 months before isolation. Splenic CD4+Foxp3(YFP/GFP)+GITRhiCD25hi Treg and CD4+Foxp3(YFP/GFP)-CD62LhiCD44lo T naive cells were double sorted using a BD FACSAria II cell sorter. The T cell subsets isolated from three individual mice in the same experimental group (genotype) was pooled into one biological replicate; three biological replicates were generated. A total of 12 samples, i.e., two genotypes, two cell cypes, and three replicates, was subjected to RNA-seq analysis. Samples were sequenced on the Illumina HiSeq 2500 to an average depth of 27.5 million 50-bp read pairs per sample.

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Konopacki C, Pritykin Y, Rubtsov Y, Leslie CS, Rudensky AY