Natural killer (NK) cells have long been thought of as a purely innate immune cell population, but increasing reports have described developmental and functional qualities of NK cells that are commonly associated with cells of the adaptive immune system. Of these features, the ability of NK cells to acquire functional qualities associated with immunological memory and continuous differentiation resulting in the formation of specific NK cell repertoires has recently been highlighted in viral infection settings. By making use of a unique cohort of monitored, at-risk intravenous drug users in this study, we were able to dissect the phenotypic and functional parameters associated with NK cell differentiation and NK cell memory in patients 3 years after acute HCV infection and either the subsequent self-clearance or progression to chronicity. We observed increased expression of cytolytic mediators and markers CD56bright and NKp46+ of NK cells in patients with chronic, but not self-limited HCV infection. Patients with a self-limited infection expressed higher levels of differentiation-associated markers CD57 and KIRs, and lower levels of NKG2A. A more extensively differentiated NK cell phenotype is associated with self-clearance in HCV patients, while the NK cells of chronic patients exhibited more naïve and effector NK cell phenotypic and functional characteristics. The identification of these distinct NK cell repertoires may shed light on the role NK cells play in determining the outcome of acute HCV infections, and the underlying immunological defects that lead to chronicity.

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Keywords Acute hepatitis, Cytotoxicity, Differentiation, Hepatitis C, Innate immunity, Memory, Natural killer cells
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Journal Journal of Viral Hepatitis
de Groen, R.A, Groothuismink, Z.M.A, van Oord, G.W, Kootstra, N.A, Janssen, H.L.A, Prins, M, … Boonstra, P.A. (2017). NK cells in self-limited HCV infection exhibit a more extensively differentiated, but not memory-like, repertoire. Journal of Viral Hepatitis. doi:10.1111/jvh.12716