title: CD4 T cell-intrinsic IL-2 signaling differentially affects Th1 and Th17 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.
authors.affiliation: Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582, Japan. hisakata@bioreg.kyushu-u.ac.jp
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Fujimura
authors.forename: Akiko
authors.initials: A
authors.lastname: Oyamada
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yoshikai
authors.forename: Hisakata
authors.initials: H
authors.lastname: Yamada
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured / Q000166:cytology; D060966:Clonal Selection, Antigen-Mediated; D000939:Epitopes; D005260:Female; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000172:deficiency; D018655:Lymphocyte Count; D038041:Lymphopoiesis / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011828:Radiation Chimera; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D018417:Th1 Cells / Q000166:cytology*; D058504:Th17 Cells / Q000166:cytology*
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; C508018:Il2ra protein, mouse; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; C111390:OVA 323-339; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin
keywords: IFN-γ; IL-17; clonal expansion; cytokine; helper T cell