title: Agonist-selected T cell development requires strong T cell receptor signaling and store-operated calcium entry.
abstract: T cell receptor (TCR) signaling driven by interaction of the TCR with specific complexes of self-peptide and the major histocompatibility complex determines T cell fate in thymic development. However, the signaling pathway through which TCR signal strength regulates distinct T cell lineages remains unknown. Here we have used mice lacking the endoplasmic reticulum Ca2+ sensors stromal interaction molecule 1 (STIM1) and STIM2 to show that STIM-induced store-operated Ca2+ entry is not essential for thymic development of conventional TCRαβ+ T cells but is specifically required for the development of agonist-selected T cells (regulatory T cells, invariant natural killer T cells, and TCRαβ+ CD8αα+ intestinal intraepithelial lymphocytes). The severe impairment of agonist-selected T cell development is mainly due to a defect in interleukin-2 (IL-2) or IL-15 signaling. Thus, STIM1 and STIM2-mediated store-operated Ca2+ influx, leading to efficient activation of NFAT (nuclear factor of activated T cells), is critical for the postselection maturation of agonist-selected T cells.
authors.affiliation: Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan. ohora.gcoe@tmd.ac.jp
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Oh-Hora
authors.forename: Noriko
authors.initials: N
authors.lastname: Komatsu
authors.forename: Mojgan
authors.initials: M
authors.lastname: Pishyareh
authors.forename: Stefan
authors.initials: S
authors.lastname: Feske
authors.forename: Shohei
authors.initials: S
authors.lastname: Hori
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Anjana
authors.initials: A
authors.lastname: Rao
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takayanagi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000276:immunology / Q000378:metabolism; D020013:Calcium Signaling / Q000276:immunology; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D017136:Ion Transport / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D050778:NFATC Transcription Factors / Q000378:metabolism*; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D019409:Interleukin-15; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D050778:NFATC Transcription Factors; D016693:Receptors, Antigen, T-Cell, alpha-beta; C100757:Stim1 protein, mouse; C525024:Stim2 protein, mouse; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D002118:Calcium