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- Title
Impaired NK-cell education diminishes resistance to murine CMV infection.
- Authors
Wei, Hairong; Nash, William T.; Makrigiannis, Andrew P.; Brown, Michael G.
- Abstract
Ly49G2 (G2+) NK cells mediate murine (M)CMV resistance in MHC Dk-expressing mice. Bone marrow transplantation (BMT) studies revealed that G2+ NK cell-mediated MCMV resistance requires Dk in both hematopoietic and nonhematopoietic cells. As a Ly49G2 ligand, Dk in both cell lineages may contribute to lysis of virus-infected cells. Alternatively, cellular differences in self-MHC Dk may have affected NK-cell education, and consequently NK cell-mediated viral clearance. We investigated the Dk-licensing effect on BM-derived NK cells in BMT recipients by analyzing cytokines, cytotoxicity and MCMV resistance. In BMT recipients with lineage-restricted Dk, 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 nonhematopoietic 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.
- Publication
European Journal of Immunology, 2014, Vol 44, Issue 11, p3273
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201444800