A voltage-gated sodium channel is essential for the positive selection of CD4<superscript>+</superscript> T cells.
In: Nature Immunology, Jg. 13 (2012-09-01), Heft 9, S. 880-887
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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 ?-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. [ABSTRACT FROM AUTHOR]
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A voltage-gated sodium channel is essential for the positive selection of CD4<superscript>+</superscript> T cells.
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Autor/in / Beteiligte Person: | Lo, Wan-Lin ; Donermeyer, David L ; Allen, Paul M |
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Zeitschrift: | Nature Immunology, Jg. 13 (2012-09-01), Heft 9, S. 880-887 |
Veröffentlichung: | 2012 |
Medientyp: | academicJournal |
ISSN: | 1529-2908 (print) |
DOI: | 10.1038/ni.2379 |
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