CD4 T cell‐intrinsic IL‐2 signaling differentially affects Th1 and Th17 development. Issue 2 (28th May 2013)

• Record Type: Journal Article
• Authors: Fujimura, Kenjiro; Oyamada, Akiko; Iwamoto, Yukihide; Yoshikai, Yasunobu; Yamada, Hisakata
• Is Part Of: Journal of leukocyte biology. Volume 94:Issue 2(2013)
• Page Start: 271
• Page End: 279
• Publication Date: 2013-05-28
• Subjects: clonal expansion -- cytokine -- helper T cell -- IL‐17 -- IFN‐γ; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.1112581
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : CD25‐deficient CD4 T cells exhibit normal Th17, but impaired Th1 development. Abstract : 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 relevance remains unclear. In addition, IL‐2‐dependent Foxp3+ CD4 Tregs suppress T cell proliferation, complicating 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‐2Rα (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 percentages of Th17 cells, it did not affect their numbers, indicating that in vitro Th17 development is also IL‐2‐independent. Th1 development was dependent on IL‐2 in vitro as well. Thus, our data suggest that cell‐intrinsic IL‐2 signaling is critical for Th1 development but plays a limited role in Th17 development in vitro as well as in vivo.