CD4 T cell-intrinsic IL-2 signaling differentially affects Th1 and Th17

IL-2 signaling is involved in clonal expansion of antigen-specific CD4 T cells. IL-2 is also reported to promote Th1 but inhibit Th17 differentiation, although in vivo rele-vance remains unclear. In addition, IL-2-dependent Foxp3 CD4 Tregs suppress T cell proliferation, com-plicating the in vivo role of IL-2 in the development of Th cell responses. To elucidate the roles of cell-intrinsic IL-2 signaling in CD4 T cells, we cotransferred TCR-Tg CD4 T cells from IL-2R (CD25)-deficient and WT mice and analyzed development of antigen-specific Th1 and Th17 responses. It was revealed that Th17 development of antigen-specific CD4 T cells was largely unaffected, whereas Th1 development was impaired by the lack of IL-2 signaling. Similar data were obtained from mixed BM chimera experiments using BM cells from CD25-deficient and WT mice. In addition, although in vitro blockade of IL-2 during Th17 development greatly increased the per-centages of Th17 cells, it did not affect their numbers, in-dicating that in vitro Th17 development is also IL-2-inde-pendent. Th1 development was dependent on IL-2 in vitro as well. Thus, our data suggest that cell-intrinsic IL-2 sig-naling is critical for Th1 development but plays a limited role in Th17 development in vitro as well as in vivo. J. Leukoc. Biol. 94: 000–000; 2013