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Shared alterations in NK cell frequency, phenotype, and function in chronic human immunodeficiency virus and hepatitis C virus infections.

Ute-Christiane Meier·Rachel E Owen·Elizabeth Taylor·Andrew Worth·Nikolai Naoumov·Christian Willberg·Kwok Tang·Phillipa Newton·Pierre Pellegrino·Ian Williams·Paul Klenerman·Persephone Borrow
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Abstract

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) cause clinically important persistent infections. The effects of virus persistence on innate immunity, including NK cell responses, and the underlying mechanisms are not fully understood. We examined the frequency, phenotype, and function of peripheral blood CD3- CD56+ NK subsets in HIV+ and HCV+ patients and identified significantly reduced numbers of total NK cells and a striking shift in NK subsets, with a marked decrease in the CD56(dim) cell fraction compared to CD56(bright) cells, in both infections. This shift influenced the phenotype and functional capacity (gamma interferon production, killing) of the total NK pool. In addition, abnormalities in the functional capacity of the CD56(dim) NK subset were observed in HIV+ patients. The shared NK alterations were found to be associated with a significant reduction in serum levels of the innate cytokine interleukin 15 (IL-15). In vitro stimulation with IL-15 rescued NK cells of HIV+ and HCV+ patients from apoptosis and enhanced proliferation and functional activity. We hypothesize that the reduced levels of IL-15 present in the serum during HIV and HCV infections might impact NK cell homeostasis, contributing to the common alterations of the NK pool observed in these unrelated infections.

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CD3 ComplexCD56 AntigenCytotoxicity, ImmunologicHIV InfectionsHepatitis CHumansInterferon-gammaInterleukin-15Killer Cells, NaturalLymphocyte SubsetsComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't

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Ute-Christiane Meier, Rachel E Owen, Elizabeth Taylor, Andrew Worth, Nikolai Naoumov, Christian Willberg, Kwok Tang, Phillipa Newton, Pierre Pellegrino, Ian Williams, Paul Klenerman, Persephone Borrow. 2005. Shared alterations in NK cell frequency, phenotype, and function in chronic human immunodeficiency virus and hepatitis C virus infections.. https://doi.org/10.1128/jvi.79.19.12365-12374.2005

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