Pathologic natural killer cell subset redistribution in HIV-1 infection: new insights in pathophysiology and clinical outcomes

• Published in: Journal of leukocyte biology Vol. 88; no. 6; pp. 1119 - 1130
• Main Authors: Brunetta, Enrico, Hudspeth, Kelly L., Mavilio, Domenico
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01-12-2010
• Subjects: Acquired Immunodeficiency Syndrome - immunology; Animals; Antibody-Dependent Cell Cytotoxicity; Antigens, Differentiation, Myelomonocytic - analysis; Antiviral activity; antiviral host responses; CD56 Antigen - analysis; Chronic infection; Cytomegalovirus Infections - immunology; HIV-1; Human immunodeficiency virus 1; Humans; Immune response; inhibitory and activating NK cell receptors; innate and adaptive immunity; Killer Cells, Natural - classification; Killer Cells, Natural - immunology; Lectins - analysis; Leukocytes; Molecular modelling; Natural killer cells; NK Cell Lectin-Like Receptor Subfamily C - analysis; Potassium channels (inwardly-rectifying); Receptors, IgG - analysis; translational immunology; Viremia
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0410225

Review discusses the clinical significance of the pathologic NK cell subset redistribution during HIV‐1 infection.
Several lines of evidence indicate that the interaction of HIV‐1 with NK cells markedly affects host immune responses and leads to a defective control of the virus. Until recently, it was generally believed that the absolute number of total circulating NK cells was decreased during the course of chronic and active phases of HIV‐1 infection and that this explained, at least in part, the defective NK cell antiviral activities. However, scientific advances made over recent years have changed this concept and have clarified that HIV‐1 viremia is associated with a pathologic redistribution rather than an absolute decrease in the number of circulating NK cells. In particular, the expansion of dysfunctional Siglec‐7neg and/or CD56neg NK cell subsets expressing an aberrant repertoire of activating and inhibitory receptors has been associated with functional impairments of NK cells and with clinical outcomes of HIV‐1 disease. Indeed, these pathologic NK cell populations often comprise the majority of NK cells in the presence of high levels of chronic HIV‐1 viremia. The reasons for these NK cell aberrancies remain unknown, as freshly purified CD4neg NK cells are not productively infected by HIV‐1. Disclosing the cellular and molecular mechanisms underlying such dysfunctions represents an important challenge of biomedical research, also considering that the presence of a rare KIR3DS1pos NK cell population represents a protective factor against HIV‐1 disease progression. In this review, we will summarize the recent updates regarding NK cell pathophysiology during the course of HIV‐1 infection.