The CD56-CD16+NK cell subset in chronic infections

Long-term human diseases can shape the immune system, and natural killer (NK) cells have been documented to differentiate into distinct subsets specifically associated with chronic virus infections. One of these subsets found in large frequencies in HIV-1 are the CD56-CD16+ NK cells, and this population's association with chronic virus infections is the subject of this review. Human NK cells are classically defined by CD56 expression, yet increasing evidence supports the NK cell status of the CD56-CD16+ subset which we discuss herein. We then discuss the evidence linking CD56-CD16+ NK cells to chronic virus infections, and the potential immunological pathways that are altered by long-term infection that could be inducing the population's differentiation. An important aspect of NK cell regulation is their interaction with human leukocyte antigen (HLA) class-I mole -cules, and we highlight work that indicates both virus and genetic-mediated variations in HLA expression that have been linked to CD56-CD16+ NK cell frequencies. Finally, we offer a perspective on CD56-CD16+ NK cell function, taking into account recent work that implies the subset is comparable to CD56+CD16+ NK cell functionality in antibody-dependent cell cytotoxicity response, and the definition of CD56-CD16+ NK cell subpo-pulations with varying degranulation capacity against target cells.

Automated summary

Long-term human diseases can affect the immune system and induce the differentiation of natural killer (NK) cells into distinct subsets, particularly in chronic virus infections such as HIV-1. This review focuses on the CD56-CD16+ NK cell subset, which is frequently found in these infections. The review discusses the evidence linking CD56-CD16+ NK cells to chronic virus infections, explores the potential immunological pathways involved in their differentiation due to long-term infection, and highlights the influence of virus and genetic-mediated variations in HLA expression on CD56-CD16+ NK cell frequencies.