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

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

Jaewon Lee ¹, Tianxiang Zhang ¹, Ilwoong Hwang ¹, Ahrom Kim ¹, Larissa Nitschke ¹, MinJae Kim ¹, Jeannine M Scott ¹, Yosuke Kamimura ², Lewis L Lanier ², Sungjin Kim ³

Affiliations

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.

PMID: 25786175 DOI: 10.1016/j.immuni.2015.02.013

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.

Name
Email *

	Sorry, but the email address you supplied was invalid.