Format

Send to

Choose Destination
Immunity. 2015 Mar 17;42(3):431-42. doi: 10.1016/j.immuni.2015.02.013.

Epigenetic modification and antibody-dependent expansion of memory-like NK cells in human cytomegalovirus-infected individuals.

Author information

1
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
2
Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA.
3
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA. Electronic address: kimsj@msu.edu.

Abstract

Long-lived "memory-like" NK cells have been identified in individuals infected by human cytomegalovirus (HCMV), but little is known about how the memory-like NK cell pool is formed. Here, we have shown that HCMV-infected individuals have several distinct subsets of memory-like NK cells that are often deficient for multiple transcription factors and signaling proteins, including tyrosine kinase SYK, for which the reduced expression was stable over time and correlated with epigenetic modification of the gene promoter. Deficient expression of these proteins was largely confined to the recently discovered FcRγ-deficient NK cells that display enhanced antibody-dependent functional activity. Importantly, FcRγ-deficient NK cells exhibited robust preferential expansion in response to virus-infected cells (both HCMV and influenza) in an antibody-dependent manner. These findings suggest that the memory-like NK cell pool is shaped and maintained by a mechanism that involves both epigenetic modification of gene expression and antibody-dependent expansion.

PMID:
25786175
PMCID:
PMC4537797
DOI:
10.1016/j.immuni.2015.02.013
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Secondary source ID, Grant support

Publication types

MeSH terms

Substances

Secondary source ID

Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center