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

Journal of Leukocyte Biology

Martha A. Alexander-Miller¹  Griffith D. Parks¹  Sean D. Reid¹  Sharad K. Sharma¹  Rama Yammani¹  Subhashini Arimilli¹ 

[1] Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USADepartment of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USADepartment of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA

关键词: CD8⁺ T cell;    function;    regulation;    NFAT;    TCR signal transduction;   

DOI  :  10.1189/jlb.0809575

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown