Pivotal Advance: Nonfunctional lung effectors exhibit decreased calcium mobilization associated with reduced expression of ORAI1

• Published in: Journal of leukocyte biology Vol. 87; no. 6; pp. 977 - 988
• Main Authors: Arimilli, Subhashini, Sharma, Sharad K., Yammani, Rama, Reid, Sean D., Parks, Griffith D., Alexander‐Miller, Martha A.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01-06-2010; The Society for Leukocyte Biology
• Subjects: Animals; Blotting, Western; Calcium - metabolism; Calcium Channels - genetics; Calcium Channels - metabolism; Calcium Signaling; CD8+ T cell; CD8-Positive T-Lymphocytes - metabolism; Cells, Cultured; Cytokines - metabolism; Electrophysiology; Female; function; Immunization; Lung - metabolism; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred BALB C; NFAT; NFATC Transcription Factors - genetics; NFATC Transcription Factors - metabolism; ORAI1 Protein; Pivotal Advance; Protein Transport; regulation; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction; Stromal Interaction Molecule 1; TCR signal transduction
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0809575

A previously unknown mechanism for the active negative regulation of function in effector T cells is described.
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.