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

• Published in: European journal of immunology 2013-12, Vol.43 (12), p.3343-3354
• Main Authors: Waite, Janelle C, Vardhana, Santosh, Shaw, Patrick J, Jang, Jung-Eun, McCarl, Christie-Ann, Cameron, Thomas O, Feske, Stefan, Dustin, Michael L
• Format: Article
• Language: English
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201243255

Entry of lymphocytes into secondary lymphoid organs (SLOs) involves intravascular arrest and intracellular calcium ion ([Ca super(2+)] sub(i)) elevation. TCR activation triggers increased [Ca super(2+)] sub(i) and can arrest T-cell motility in vitro. However, the requirement for [Ca super(2+)] sub(i) elevation in arresting T cells in vivo has not been tested. Here, we have manipulated the Ca super(2+) release-activated Ca super(2+) (CRAC) channel pathway required for [Ca super(2+)] sub(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 naive CD4 super(+) T cells to SLOs and only moderately reduced crawling speeds in vivo. T cells expressing ORAI1-DN lacked TCR activation induced [Ca super(2+)] sub(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.