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NK cells negatively regulate CD8 T cells via natural cytotoxicity receptor (NCR) 1 during LCMV infection

Katharina Pallmer1, Isabel Barnstorf1, Nicolas S Baumann1

  • 1Institute of Microbiology, ETH Zürich, Zürich, Switzerland.

Plos Pathogens
|April 18, 2019
PubMed

Insights

Natural killer (NK) cells regulate antiviral CD8 T cell responses. The activating receptor natural cytotoxicity receptor (NCR) 1 deficiency boosts CD8 T cell activity, enhancing viral control but causing immunopathology.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Natural killer (NK) cells are crucial for innate immunity against viral infections.
  • NK cells also influence adaptive immune responses, but their regulatory mechanisms on CD8 T cells are not fully understood.
  • The role of natural cytotoxicity receptor (NCR) 1 in NK cell-mediated regulation of antiviral CD8 T cell immunity requires further investigation.

Purpose of the Study:

  • To elucidate the mechanisms by which NK cells, specifically through NCR1, regulate virus-specific CD8 T cell responses.
  • To investigate the impact of NCR1 deficiency on CD8 T cell activation, viral control, and immunopathology during LCMV infection.

Main Methods:

  • Utilized activating receptor natural cytotoxicity receptor (NCR) 1 deficient (NCR1gfp/gfp) mice for LCMV infection studies.
  • Performed transfer experiments of virus-specific CD8 T cells into NCR1 deficient hosts.
  • Analyzed splenic microarchitecture and quantified virus-specific CD8 T cells and their activation status.

Main Results:

  • NCR1 deficiency led to increased numbers and enhanced activation of virus-specific CD8 T cells during acute and chronic LCMV infection.
  • Absence of NCR1 resulted in exacerbated immunopathology, including weight loss, and improved viral control.
  • Demonstrated direct cross-talk between NK cells and CD8 T cells, with NK cells eliminating activated CD8 T cells via NCR1.

Conclusions:

  • NK cells, via NCR1, directly recognize and eliminate activated CD8 T cells early in viral infections.
  • This novel regulatory pathway prevents an overshooting T cell response, mitigating immunopathology.
  • NCR1 plays a critical role in balancing effective viral clearance and immune homeostasis.

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