TY  - JOUR
AU  - Kared, H
AU  - Martelli, S
AU  - Tan, SW
AU  - Simoni, Y
AU  - Chong, ML
AU  - Yap, SH
AU  - Newell, EW
AU  - Pender, SLF
AU  - Kamaruizaman, A
AU  - Rajasuriar, R
AU  - Larbi, A
Y2  - 2020/12/10
Y1  - 2018/04/20
SN  - 1664-3224
UR  - http://hdl.handle.net/11343/253731
AB  - 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.
LA  - English
PB  - FRONTIERS MEDIA SA
T1  - Adaptive NKG2C(+)CD57(+) Natural Killer Cell and Tim-3 Expression During Viral Infections
DO  - 10.3389/fimmu.2018.00686
IS  - Frontiers in Immunology
VL  - 9
IS  - APR
L1  - /bitstream/handle/11343/253731/PMC5919961.pdf?sequence=1&isAllowed=y
ER  -