Murine natural killer cell licensing and regulation by T regulatory cells in viral responses

Can M. Sungur, Yajarayma J. Tang-Feldman, Erik Ames, Maite Alvarez, Mingyi Chen, Dan L. Longo, Claire Pomeroy, William J Murphy

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Natural killer (NK) cells show differential functionality based on their capability of binding to self-MHC consistent with licensing. Here we show in vivo confirmation of the physiologic effects of licensing with differential effects of NK subsets on anti-murine cytomegalovirus (anti-MCMV) responses after syngeneic hematopoietic stem cell transplantation (HSCT) or regulatory T-cell (Treg) depletion. After HSCT, depletion of licensed NK cells led to far greater viral loads in target organs early after infection compared with nondepleted and unlicensed depleted mice. There was a preferential expansion of licensed, C-type lectin-like activating receptor Ly49H+ NK cells with increased IFNγ production after infection in nondepleted mice post-HSCT and after Treg depletion. Adoptive transfer of licensed NK subsets into immunodeficient hosts provided significantly greater MCMV resistance compared with transfer of total NK populations or unlicensed subsets. In non-HSCT mice, only concurrent depletion of Tregs or TGF-β neutralization resulted in detection of NK licensing effects. This suggests that licensed NK cells are the initial and rapidly responding population of NK cells to MCMV infection, but are highly regulated by Tregs and TGF-β.

Original languageEnglish (US)
Pages (from-to)7401-7406
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number18
DOIs
StatePublished - Apr 30 2013

Keywords

  • Arming
  • Education
  • Immunity
  • Innate immune system
  • Virology

ASJC Scopus subject areas

  • General

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