Adaptive NKG2C+CD57+ Natural Killer Cell and Tim-3 Expression During Viral Infections

Repetitive stimulation by persistent pathogens such as human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV) induces the differentiation of natural killer (NK) cells. This maturation pathway is characterized by the acquisition of phenotypic markers, CD2, CD57, and NKG2C, and effector fu...

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Main Authors: Kared, Hassen, Martelli, Serena, Tan, Shu Wen, Simoni, Yannick, Chong, Meng Li, Yap, Siew Hwei, Newell, Evan W., Pender, Sylvia L. F., Kamarulzaman, Adeeba, Rajasuriar, Reena, Larbi, Anis
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Published: Frontiers Media 2018
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author Kared, Hassen
Martelli, Serena
Tan, Shu Wen
Simoni, Yannick
Chong, Meng Li
Yap, Siew Hwei
Newell, Evan W.
Pender, Sylvia L. F.
Kamarulzaman, Adeeba
Rajasuriar, Reena
Larbi, Anis
author_facet Kared, Hassen
Martelli, Serena
Tan, Shu Wen
Simoni, Yannick
Chong, Meng Li
Yap, Siew Hwei
Newell, Evan W.
Pender, Sylvia L. F.
Kamarulzaman, Adeeba
Rajasuriar, Reena
Larbi, Anis
author_sort Kared, Hassen
collection UM
description Repetitive stimulation by persistent pathogens such as human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV) induces the differentiation of natural killer (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, promyelocytic leukemia zinc finger protein, and Foxo3. Here, we show that persistent immune activation during chronic viral co-infections (HCMV, hepatitis C virus, and 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.
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spelling um.eprints-216902019-07-22T06:21:45Z http://eprints.um.edu.my/21690/ Adaptive NKG2C+CD57+ Natural Killer Cell and Tim-3 Expression During Viral Infections Kared, Hassen Martelli, Serena Tan, Shu Wen Simoni, Yannick Chong, Meng Li Yap, Siew Hwei Newell, Evan W. Pender, Sylvia L. F. Kamarulzaman, Adeeba Rajasuriar, Reena Larbi, Anis QH Natural history R Medicine Repetitive stimulation by persistent pathogens such as human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV) induces the differentiation of natural killer (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, promyelocytic leukemia zinc finger protein, and Foxo3. Here, we show that persistent immune activation during chronic viral co-infections (HCMV, hepatitis C virus, and 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. Frontiers Media 2018 Article PeerReviewed Kared, Hassen and Martelli, Serena and Tan, Shu Wen and Simoni, Yannick and Chong, Meng Li and Yap, Siew Hwei and Newell, Evan W. and Pender, Sylvia L. F. and Kamarulzaman, Adeeba and Rajasuriar, Reena and Larbi, Anis (2018) Adaptive NKG2C+CD57+ Natural Killer Cell and Tim-3 Expression During Viral Infections. Frontiers in Immunology, 9. p. 686. ISSN 1664-3224, DOI https://doi.org/10.3389/fimmu.2018.00686 <https://doi.org/10.3389/fimmu.2018.00686>. https://doi.org/10.3389/fimmu.2018.00686 doi:10.3389/fimmu.2018.00686
spellingShingle QH Natural history
R Medicine
Kared, Hassen
Martelli, Serena
Tan, Shu Wen
Simoni, Yannick
Chong, Meng Li
Yap, Siew Hwei
Newell, Evan W.
Pender, Sylvia L. F.
Kamarulzaman, Adeeba
Rajasuriar, Reena
Larbi, Anis
Adaptive NKG2C+CD57+ Natural Killer Cell and Tim-3 Expression During Viral Infections
title Adaptive NKG2C+CD57+ Natural Killer Cell and Tim-3 Expression During Viral Infections
title_full Adaptive NKG2C+CD57+ Natural Killer Cell and Tim-3 Expression During Viral Infections
title_fullStr Adaptive NKG2C+CD57+ Natural Killer Cell and Tim-3 Expression During Viral Infections
title_full_unstemmed Adaptive NKG2C+CD57+ Natural Killer Cell and Tim-3 Expression During Viral Infections
title_short Adaptive NKG2C+CD57+ Natural Killer Cell and Tim-3 Expression During Viral Infections
title_sort adaptive nkg2c cd57 natural killer cell and tim 3 expression during viral infections
topic QH Natural history
R Medicine
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