title: Pivotal Advance: Nonfunctional lung effectors exhibit decreased calcium mobilization associated with reduced expression of ORAI1.
abstract: CD8(+) T cells play a critical role in the clearance of respiratory pathogens. Thus, it is surprising that functional inactivation of lung effectors has been observed in many models of viral infection. Currently, the molecular defect responsible for the shut-off of function in these cells is unknown. In the present study, we addressed this question using a model of respiratory infection with the paramyxovirus SV5. Nonfunctional cells were found to exhibit decreases in SOCE, resulting in reduced NFAT1 activation. Notably, function could be restored by the provision of increased levels of extracellular calcium. The reduced ability to mobilize calcium was associated with reduced expression of ORAI1, the CRAC channel subunit. These findings reveal a previously unknown mechanism for the negative regulation of function in effector T cells.
authors.affiliation: 1. Room 5140 Gray Building, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA.
authors.forename: Subhashini
authors.initials: S
authors.lastname: Arimilli
authors.forename: Sharad K
authors.initials: SK
authors.lastname: Sharma
authors.forename: Rama
authors.initials: R
authors.lastname: Yammani
authors.forename: Sean D
authors.initials: SD
authors.lastname: Reid
authors.forename: Griffith D
authors.initials: GD
authors.lastname: Parks
authors.forename: Martha A
authors.initials: MA
authors.lastname: Alexander-Miller
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004594:Electrophysiology; D005260:Female; D007114:Immunization; D008168:Lung / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071740:ORAI1 Protein; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D016207:Cytokines; D008562:Membrane Glycoproteins; D050778:NFATC Transcription Factors; C494007:Nfatc2 protein, mouse; D000071740:ORAI1 Protein; C520430:Orai1 protein, mouse; D012333:RNA, Messenger; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D002118:Calcium