Interference with Ca(2+) release activated Ca(2+) (CRAC) channel function delays T-cell arrest in vivo

Eur J Immunol. 2013 Dec;43(12):3343-54. doi: 10.1002/eji.201243255. Epub 2013 Sep 6.


Entry of lymphocytes into secondary lymphoid organs (SLOs) involves intravascular arrest and intracellular calcium ion ([Ca(2+)]i) elevation. TCR activation triggers increased [Ca(2+)]i and can arrest T-cell motility in vitro. However, the requirement for [Ca(2+)]i elevation in arresting T cells in vivo has not been tested. Here, we have manipulated the Ca(2+) release-activated Ca(2+) (CRAC) channel pathway required for [Ca(2+)]i elevation in T cells through genetic deletion of stromal interaction molecule (STIM) 1 or by expression of a dominant-negative ORAI1 channel subunit (ORAI1-DN). Interestingly, the absence of CRAC did not interfere with homing of naïve CD4(+) T cells to SLOs and only moderately reduced crawling speeds in vivo. T cells expressing ORAI1-DN lacked TCR activation induced [Ca(2+)]i elevation, yet arrested motility similar to control T cells in vitro. In contrast, antigen-specific ORAI1-DN T cells had a twofold delayed onset of arrest following injection of OVA peptide in vivo. CRAC channel function is not required for homing to SLOs, but enhances spatiotemporal coordination of TCR signaling and motility arrest.

Keywords: Antigen recognition; Calcium signaling; Intravital microscopy; T‐cell activation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Calcium / immunology*
  • Calcium Channels / genetics
  • Calcium Channels / immunology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Knockout
  • ORAI1 Protein
  • Peptides / immunology
  • Peptides / pharmacology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Stromal Interaction Molecule 1


  • Calcium Channels
  • Membrane Glycoproteins
  • ORAI1 Protein
  • Orai1 protein, mouse
  • Peptides
  • Receptors, Antigen, T-Cell
  • Stim1 protein, mouse
  • Stromal Interaction Molecule 1
  • Calcium