A voltage-gated sodium channel is essential for the positive selection of CD4(+) T cells
In: Nature immunology, Jg. 13 (2012-04-23), Heft 9
Online
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Zugriff:
The sustained entry of Ca(2+) 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 Ca(2+) 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 β-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 Ca(2+) signals required for CD4(+) T cell development.
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A voltage-gated sodium channel is essential for the positive selection of CD4(+) T cells
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Autor/in / Beteiligte Person: | Lo, Wan-Lin ; Allen, Paul M. ; Donermeyer, David L. |
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Zeitschrift: | Nature immunology, Jg. 13 (2012-04-23), Heft 9 |
Veröffentlichung: | 2012 |
Medientyp: | unknown |
ISSN: | 1529-2916 (print) |
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