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

First Author  Sungur CM Year  2013
Journal  Proc Natl Acad Sci U S A Volume  110
Issue  18 Pages  7401-6
PubMed ID  23589894 Mgi Jnum  J:196662
Mgi Id  MGI:5489001 Doi  10.1073/pnas.1218767110
Citation  Sungur CM, et al. (2013) Murine natural killer cell licensing and regulation by T regulatory cells in viral responses. Proc Natl Acad Sci U S A 110(18):7401-6
abstractText  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 IFNgamma 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-beta 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-beta.
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