Natural killer (NK) cells play an important role in the host defence against pathogens and cancer. NK cell function is tightly regulated by signals from activating and inhibitory receptors. The receptor repertoire of NK cells is shaped by maturation and the exposure to various environmental factors including viral infection, resulting in a remarkable degree of NK cell diversity. Further, recent data from studies in mice suggests that NK cells can acquire a memory phenotype, however, human data is sparse.
This thesis describes the NK cells changes that result from chronic hepatitis B virus (HBV) infection. This includes (1) the identification of a novel KLRG1+ NK cell subset with antifibrotic capabilities, (2) first in human description of memory NK cells sharing the cardinal features of immune memory such as antigen specificity and longevity, and (3) the evolution of an inhibited dysfunctional CD56neg NK cells subset including in-depth functional studies.
Overall, this thesis identified the novel roles of human NK cells, specifically in the context of hepatitis B infection. These findings, particularly those relating to anti-fibrotic NK cells and memory NK cells provide novel cellular targets to stop liver fibrosis progression and potentially eradicate hepatitis B. Further, such concepts could be translated to other chronic infections or cancer.