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- Title
A voltage-gated sodium channel is essential for the positive selection of CD4<sup>+</sup> T cells.
- Authors
Lo, Wan-Lin; Donermeyer, David L; Allen, Paul M
- Abstract
The sustained entry of Ca2+ into CD4+CD8+ double-positive thymocytes is required for positive selection. Here we identified a voltage-gated Na+ channel (VGSC) that was essential for positive selection of CD4+ T cells. Pharmacological inhibition of VGSC activity inhibited the sustained Ca2+ influx induced by positively selecting ligands and the in vitro positive selection of CD4+ but not CD8+ T cells. In vivo short hairpin RNA (shRNA)-mediated knockdown of the gene encoding a regulatory ?-subunit of a VGSC specifically inhibited the positive selection of CD4+ T cells. Ectopic expression of VGSC in peripheral AND CD4+ T cells bestowed the ability to respond to a positively selecting ligand, which directly demonstrated that VGSC expression was responsible for the enhanced sensitivity. Thus, active VGSCs in thymocytes provide a mechanism by which a weak positive selection signal can induce the sustained Ca2+ signals required for CD4+ T cell development.
- Publication
Nature Immunology, 2012, Vol 13, Issue 9, p880
- ISSN
1529-2908
- Publication type
Academic Journal
- DOI
10.1038/ni.2379