| First Author | Lo WL | Year | 2012 |
| Journal | Nat Immunol | Volume | 13 |
| Issue | 9 | Pages | 880-7 |
| PubMed ID | 22842345 | Mgi Jnum | J:187595 |
| Mgi Id | MGI:5437533 | Doi | 10.1038/ni.2379 |
| Citation | Lo WL, et al. (2012) A voltage-gated sodium channel is essential for the positive selection of CD4(+) T cells. Nat Immunol 13(9):880-7 |
| abstractText | 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 beta-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. |
