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Immunity. 2013 May 23;38(5):881-95. doi: 10.1016/j.immuni.2013.02.008. Epub 2013 Mar 14.

Agonist-selected T cell development requires strong T cell receptor signaling and store-operated calcium entry.

Author information

1
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

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.

PMID:
23499491
PMCID:
PMC3669219
DOI:
10.1016/j.immuni.2013.02.008
[Indexed for MEDLINE]
Free PMC Article

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