Tissue-protective effects of NKG2A in immune-mediated clearance of virus infection

Kenneth H. Ely*, Mitsuo Matsuoka, Matthew DeBerge, Jessica A. Ruby, Jun Liu, Mark J. Schneider, Yan Wang, Young S. Hahn, Richard I. Enelow

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Virus infection triggers a CD8+T cell response that aids in virus clearance, but also expresses effector functions that may result in tissue injury. CD8+T cells express a variety of activating and inhibiting ligands, though regulation of the expression of inhibitory receptors is not well understood. The ligand for the inhibitory receptor, NKG2A, is the non-classical MHC-I molecule Qa1b, which may also serve as a putative restricting element for the T cell receptors of purported regulatory CD8+T cells. We have previously shown that Qa1b-null mice suffer considerably enhanced immunopathologic lung injury in the context of CD8+T cell-mediated clearance of influenza infection, as well as evidence in a non-viral system that failure to ligate NKG2A on CD8+effector T cells may represent an important component of this process. In this report, we examine the requirements for induction of NKG2A expression, and show that NKG2A expression by CD8+T cells occurs as a result of migration from the MLN to the inflammatory lung environment, irrespective of peripheral antigen recognition. Further, we confirmed that NKG2A is a mediator in limiting immunopathology in virus infection using mice with a targeted deletion of NKG2A, and infecting the mutants with two different viruses, influenza and adenovirus. In neither infection is virus clearance altered. In influenza infection, the enhanced lung injury was associated with increased chemoattractant production, increased infiltration of inflammatory cells, and significantly enhanced alveolar hemorrhage. The primary mechanism of enhanced injury was the loss of negative regulation of CD8+T cell effector function. A similar effect was observed in the livers of mutant mice infected intravenously with adenovirus. These results demonstrate the immunoregulatory role of CD8+NKG2A expression in virus infection, which negatively regulates T cell effector functions and contributes to protection of tissue integrity during virus clearance.

Original languageEnglish (US)
Article numbere108385
JournalPloS one
Volume9
Issue number9
DOIs
StatePublished - Sep 24 2014

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T-cells
Virus Diseases
Viruses
protective effect
T-lymphocytes
Tissue
T-Lymphocytes
viruses
infection
Lung Injury
Adenoviridae
Human Influenza
lungs
NK Cell Lectin-Like Receptor Subfamily C
influenza
receptors
Ligands
mice
Chemotactic Factors
Wounds and Injuries

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Ely, K. H., Matsuoka, M., DeBerge, M., Ruby, J. A., Liu, J., Schneider, M. J., ... Enelow, R. I. (2014). Tissue-protective effects of NKG2A in immune-mediated clearance of virus infection. PloS one, 9(9), [e108385]. https://doi.org/10.1371/journal.pone.0108385
Ely, Kenneth H. ; Matsuoka, Mitsuo ; DeBerge, Matthew ; Ruby, Jessica A. ; Liu, Jun ; Schneider, Mark J. ; Wang, Yan ; Hahn, Young S. ; Enelow, Richard I. / Tissue-protective effects of NKG2A in immune-mediated clearance of virus infection. In: PloS one. 2014 ; Vol. 9, No. 9.
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Ely, KH, Matsuoka, M, DeBerge, M, Ruby, JA, Liu, J, Schneider, MJ, Wang, Y, Hahn, YS & Enelow, RI 2014, 'Tissue-protective effects of NKG2A in immune-mediated clearance of virus infection', PloS one, vol. 9, no. 9, e108385. https://doi.org/10.1371/journal.pone.0108385

Tissue-protective effects of NKG2A in immune-mediated clearance of virus infection. / Ely, Kenneth H.; Matsuoka, Mitsuo; DeBerge, Matthew; Ruby, Jessica A.; Liu, Jun; Schneider, Mark J.; Wang, Yan; Hahn, Young S.; Enelow, Richard I.

In: PloS one, Vol. 9, No. 9, e108385, 24.09.2014.

Research output: Contribution to journalArticle

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T1 - Tissue-protective effects of NKG2A in immune-mediated clearance of virus infection

AU - Ely, Kenneth H.

AU - Matsuoka, Mitsuo

AU - DeBerge, Matthew

AU - Ruby, Jessica A.

AU - Liu, Jun

AU - Schneider, Mark J.

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AU - Hahn, Young S.

AU - Enelow, Richard I.

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