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Eur J Immunol. 2014 Nov;44(11):3273-82. doi: 10.1002/eji.201444800. Epub 2014 Oct 1.

Impaired NK-cell education diminishes resistance to murine CMV infection.

Author information

1
Department of Medicine, Beirne B. Carter Center for Immunology Research, University of Virginia School of Medicine, Charlottesville, Virginia, USA.

Abstract

Ly49G2 (G2+) NK cells mediate murine (M)CMV resistance in MHC D(k) -expressing mice. Bone marrow transplantation (BMT) studies revealed that G2+ NK cell-mediated MCMV resistance requires D(k) in both hematopoietic and nonhematopoietic cells. As a Ly49G2 ligand, D(k) in both cell lineages may contribute to lysis of virus-infected cells. Alternatively, cellular differences in self-MHC D(k) may have affected NK-cell education, and consequently NK cell-mediated viral clearance. We investigated the D(k) -licensing effect on BM-derived NK cells in BMT recipients by analyzing cytokines, cytotoxicity and MCMV resistance. In BMT recipients with lineage-restricted D(k) , G2+ NK-cell reactivity and cytotoxicity was diminished in comparison to BMT recipients with self-MHC in all cells. Reduced G2+ NK-mediated MCMV resistance in BMT recipients with lineage-restricted self-MHC indicates that licensing of G2+ NK cells is related to NK-cell reactivity and viral control. Titrating donor BM with self-MHC-bearing hematopoietic cells, as well as adoptive transfer of mature G2+ NK cells into BMT recipients with self-MHC in non-hematopoietic cells only, enhanced NK-cell licensing and rescued MCMV resistance. This disparate self-MHC NK-cell education model would suggest that inadequately licensed NK cells corresponded to inefficient viral sensing and clearance.

KEYWORDS:

Allogeneic transplantation; Ly49G2; MHC; NKp46

PMID:
25187217
PMCID:
PMC4233007
DOI:
10.1002/eji.201444800
[Indexed for MEDLINE]
Free PMC Article

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