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.

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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