Histone Deacetylase Inhibitors Enhance CD4 T Cell Susceptibility to NK Cell Killing but Reduce NK Cell Function

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Title: Histone Deacetylase Inhibitors Enhance CD4 T Cell Susceptibility to NK Cell Killing but Reduce NK Cell Function
Authors: Pace, M
Williams, J
Kurioka, A
Gerry, AB
Jakobsen, B
Klenerman, P
Nwokolo, N
Fox, J
Fidler, S
Frater, J
CHERUB Investigators
Item Type: Journal Article
Abstract: In the search for a cure for HIV-1 infection, histone deacetylase inhibitors (HDACi) are being investigated as activators of latently infected CD4 T cells to promote their targeting by cytotoxic T-lymphocytes (CTL). However, HDACi may also inhibit CTL function, suggesting different immunotherapy approaches may need to be explored. Here, we study the impact of different HDACi on both Natural Killer (NK) and CTL targeting of HIV-1 infected cells. We found HDACi down-regulated HLA class I expression independently of HIV-1 Nef which, without significantly compromising CTL function, led to enhanced targeting by NK cells. HDACi-treated HIV-1-infected CD4 T cells were also more effectively cleared than untreated controls during NK co-culture. However, HDACi impaired NK function, reducing degranulation and killing capacity. Depending on the HDACi and dose, this impairment could counteract the benefit gained by treating infected target cells. These data suggest that following HDACi-induced HLA class I down-regulation NK cells kill HIV-1-infected cells, although HDACi-mediated NK cell inhibition may negate this effect. Our data emphasize the importance of studying the effects of potential interventions on both targets and effectors.
Issue Date: 16-Aug-2016
Date of Acceptance: 30-Jun-2016
ISSN: 1553-7366
Publisher: Public Library of Science
Journal / Book Title: PLOS Pathogens
Volume: 12
Issue: 8
Copyright Statement: © 2016 Pace et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: CHERUB Investigators
0605 Microbiology
1107 Immunology
1108 Medical Microbiology
Publication Status: Published
Article Number: e1005782
Appears in Collections:Department of Medicine
Faculty of Medicine

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