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Updated: Jun 16, 2026

Isolation of Human Myoblasts, Assessment of Myogenic Differentiation, and Store-operated Calcium Entry Measurement
Published on: July 26, 2017
Pivotal Advance: Nonfunctional lung effectors exhibit decreased calcium mobilization associated with reduced
Subhashini Arimilli1, Sharad K Sharma, Rama Yammani
11. Room 5140 Gray Building, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA.
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.
Insights
Functional inactivation of lung effector CD8(+) T cells during viral infections is linked to reduced calcium signaling. Restoring extracellular calcium levels and ORAI1 expression can reverse this functional defect.
Area of Science:
- Immunology
- Virology
- Cellular Biology
Background:
- CD8(+) T cells are crucial for clearing respiratory pathogens.
- Functional inactivation of lung effector T cells occurs during viral infections.
- The molecular mechanisms underlying this T cell dysfunction remain unclear.
Purpose of the Study:
- To investigate the molecular basis for functional inactivation of lung effector T cells during viral infections.
- To identify the specific defects leading to T cell dysfunction in the context of respiratory viral infections.
Main Methods:
- Utilized a mouse model of respiratory infection with the paramyxovirus SV5.
- Assessed the function of CD8(+) T cells, including calcium signaling (SOCE) and NFAT1 activation.
- Quantified ORAI1 expression in T cells.
- Investigated the effect of extracellular calcium levels on T cell function.
Main Results:
- Nonfunctional CD8(+) T cells exhibited decreased store-operated calcium entry (SOCE).
- Reduced SOCE correlated with diminished NFAT1 activation.
- T cell function could be restored by increasing extracellular calcium.
- Decreased ORAI1 expression was observed in nonfunctional T cells, impacting calcium mobilization.
Conclusions:
- Reduced ORAI1 expression leads to impaired calcium mobilization and SOCE in effector T cells during viral infections.
- This calcium signaling defect results in functional inactivation of CD8(+) T cells.
- The findings reveal a novel mechanism of T cell immune evasion by respiratory viruses.
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