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

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

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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.

Item Type: Article
Uncontrolled Keywords: Aging; Cancer; Checkpoint blockade; Chronic infection; Exhaustion; Maturation; Natural killer cells; Senescence
Subjects: Q Science > QH Natural history
R Medicine
Divisions: Faculty of Medicine
Centre of Excellence for Research in AIDS (CERiA)
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 22 Jul 2019 06:21
Last Modified: 22 Jul 2019 06:21

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