SIV-induced terminally differentiated adaptive NK cells in lymph nodes associated with enhanced MHC-E restricted activity

Nat Commun. 2021 Feb 24;12(1):1282. doi: 10.1038/s41467-021-21402-1.

Abstract

Natural killer (NK) cells play a critical understudied role during HIV infection in tissues. In a natural host of SIV, the African green monkey (AGM), NK cells mediate a strong control of SIVagm infection in secondary lymphoid tissues. We demonstrate that SIVagm infection induces the expansion of terminally differentiated NKG2alow NK cells in secondary lymphoid organs displaying an adaptive transcriptional profile and increased MHC-E-restricted cytotoxicity in response to SIV Env peptides while expressing little IFN-γ. Such NK cell differentiation was lacking in SIVmac-infected macaques. Adaptive NK cells displayed no increased NKG2C expression. This study reveals a previously unknown profile of NK cell adaptation to a viral infection, thus accelerating strategies toward NK-cell directed therapies and viral control in tissues.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Chlorocebus aethiops
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • K562 Cells
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / metabolism*
  • Lymph Nodes / metabolism*
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / metabolism
  • Macaca
  • Male
  • NK Cell Lectin-Like Receptor Subfamily C / metabolism*
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Immunodeficiency Virus / immunology
  • Simian Immunodeficiency Virus / pathogenicity
  • Transcriptome / genetics

Substances

  • Klrc2 protein, mouse
  • NK Cell Lectin-Like Receptor Subfamily C