Defective survival of naive CD8+ T lymphocytes in the absence of the beta3 regulatory subunit of voltage-gated calcium channels

Nat Immunol. 2009 Dec;10(12):1275-82. doi: 10.1038/ni.1793. Epub 2009 Oct 18.


The survival of T lymphocytes requires sustained, Ca(2+) influx-dependent gene expression. The molecular mechanism that governs sustained Ca(2+) influx in naive T lymphocytes is unknown. Here we report an essential role for the beta3 regulatory subunit of voltage-gated calcium (Ca(v)) channels in the maintenance of naive CD8(+) T cells. Deficiency in beta3 resulted in a profound survival defect of CD8(+) T cells. This defect correlated with depletion of the pore-forming subunit Ca(v)1.4 and attenuation of T cell antigen receptor (TCR)-mediated global Ca(2+) entry in CD8(+) T cells. Ca(v)1.4 and beta3 associated with T cell signaling machinery and Ca(v)1.4 localized in lipid rafts. Our data demonstrate a mechanism by which Ca(2+) entry is controlled by a Ca(v)1.4-beta3 channel complex in T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Calcium Channels / deficiency*
  • Calcium Channels / genetics
  • Calcium Channels / immunology*
  • Calcium Channels / metabolism
  • Calcium Channels, L-Type
  • Calcium Signaling
  • Cell Survival
  • Gene Expression Regulation
  • Homeostasis
  • Immunity, Innate*
  • Mice
  • Mice, Knockout
  • fas Receptor / metabolism


  • Cacna1f protein, mouse
  • Cacnb3 protein, mouse
  • Calcium Channels
  • Calcium Channels, L-Type
  • fas Receptor