The University of Southampton
University of Southampton Institutional Repository
Warning ePrints Soton is experiencing an issue with some file downloads not being available. We are working hard to fix this. Please bear with us.

Adaptive NKG2C+ CD57+ Natural Killer cell and Tim-3 expression during viral infections

Adaptive NKG2C+ CD57+ Natural Killer cell and Tim-3 expression during viral infections
Adaptive NKG2C+ CD57+ Natural Killer cell and Tim-3 expression during viral infections
Repetitive stimulation by persistent pathogens such as HCMV or HIV induces the differentiation of NK cells. This maturation pathway is characterized by the acquisition of phenotypic markers, CD2, CD57 and NKG2C, and effector functions – a process regulated by Tim-3 and orchestrated by a complex network of transcriptional factors, involving T-bet, Eomes, Zeb2, PLZF, and Foxo3. Here, we show that persistent immune activation during chronic viral co-infections (HCMV, HCV, HIV) interferes with the functional phenotype of NK cells by modulating the Tim-3 pathway; a decrease in Tim-3 expression combined with the acquisition of inhibitory receptors skewed NK cells toward an exhausted and cytotoxic phenotype in an inflammatory environment during chronic HIV infection. A better understanding of the mechanisms underlying NK cell differentiation could aid the identification of new immunological targets for checkpoint blockade therapies in a manner that is relevant to chronic infection and cancer.
1664-3224
Kared, Hassen
f8fded21-31be-4eb6-b41d-9f47d9879bb4
Martelli, Serena
3a6d7c3d-1972-4b5b-ada0-45f0247a763f
Tan, Shu
5d3bad44-1a8a-4099-af1c-c79ee3f3a8d3
Simoni, Yannick
b9f70b13-4757-4f36-9837-32f51e04c102
Chong, Meng Li
81d0567b-54e2-43d7-bae5-cc914531c404
Yap, Siew Hwei
af96af06-eadd-42e5-8048-0c7f44e5f39d
Newell, Evan W.
8e61366d-64f5-4ae2-8660-d73de4475ebe
Pender, Sylvia
62528b03-ec42-41bb-80fe-48454c2c5242
Kamarulzaman, Adeeba
92cd1ffd-c81b-4a44-bc35-b78b1adde37a
Rajasuriar, Reena
8d8fc9a9-a1b2-4c51-9a7c-9445c7de8d9e
Larbi, Anis
e25e63f4-bd55-40e0-915f-aaf85efe1263
Kared, Hassen
f8fded21-31be-4eb6-b41d-9f47d9879bb4
Martelli, Serena
3a6d7c3d-1972-4b5b-ada0-45f0247a763f
Tan, Shu
5d3bad44-1a8a-4099-af1c-c79ee3f3a8d3
Simoni, Yannick
b9f70b13-4757-4f36-9837-32f51e04c102
Chong, Meng Li
81d0567b-54e2-43d7-bae5-cc914531c404
Yap, Siew Hwei
af96af06-eadd-42e5-8048-0c7f44e5f39d
Newell, Evan W.
8e61366d-64f5-4ae2-8660-d73de4475ebe
Pender, Sylvia
62528b03-ec42-41bb-80fe-48454c2c5242
Kamarulzaman, Adeeba
92cd1ffd-c81b-4a44-bc35-b78b1adde37a
Rajasuriar, Reena
8d8fc9a9-a1b2-4c51-9a7c-9445c7de8d9e
Larbi, Anis
e25e63f4-bd55-40e0-915f-aaf85efe1263

Kared, Hassen, Martelli, Serena, Tan, Shu, Simoni, Yannick, Chong, Meng Li, Yap, Siew Hwei, Newell, Evan W., Pender, Sylvia, Kamarulzaman, Adeeba, Rajasuriar, Reena and Larbi, Anis (2018) Adaptive NKG2C+ CD57+ Natural Killer cell and Tim-3 expression during viral infections. Frontiers in Immunology, 9, [686]. (doi:10.3389/fimmu.2018.00686).

Record type: Article

Abstract

Repetitive stimulation by persistent pathogens such as HCMV or HIV induces the differentiation of NK cells. This maturation pathway is characterized by the acquisition of phenotypic markers, CD2, CD57 and NKG2C, and effector functions – a process regulated by Tim-3 and orchestrated by a complex network of transcriptional factors, involving T-bet, Eomes, Zeb2, PLZF, and Foxo3. Here, we show that persistent immune activation during chronic viral co-infections (HCMV, HCV, HIV) interferes with the functional phenotype of NK cells by modulating the Tim-3 pathway; a decrease in Tim-3 expression combined with the acquisition of inhibitory receptors skewed NK cells toward an exhausted and cytotoxic phenotype in an inflammatory environment during chronic HIV infection. A better understanding of the mechanisms underlying NK cell differentiation could aid the identification of new immunological targets for checkpoint blockade therapies in a manner that is relevant to chronic infection and cancer.

Text
334396_Kared_Manuscript - Accepted Manuscript
Available under License Creative Commons Attribution.
Download (10MB)

More information

Accepted/In Press date: 20 March 2018
e-pub ahead of print date: 20 April 2018
Published date: 20 April 2018

Identifiers

Local EPrints ID: 418828
URI: http://eprints.soton.ac.uk/id/eprint/418828
ISSN: 1664-3224
PURE UUID: d7177bb2-569c-4586-a749-c2dc50d33ace
ORCID for Sylvia Pender: ORCID iD orcid.org/0000-0001-6332-0333

Catalogue record

Date deposited: 23 Mar 2018 17:30
Last modified: 26 Nov 2021 02:44

Export record

Altmetrics

Contributors

Author: Hassen Kared
Author: Serena Martelli
Author: Shu Tan
Author: Yannick Simoni
Author: Meng Li Chong
Author: Siew Hwei Yap
Author: Evan W. Newell
Author: Sylvia Pender ORCID iD
Author: Adeeba Kamarulzaman
Author: Reena Rajasuriar
Author: Anis Larbi

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×