title: IL-10 induces aberrant deletion of dendritic cells by natural killer cells in the context of HIV infection.
abstract: Persistent levels of IL-10 play a central role in progressive immune dysfunction associated with chronic viral infections such as HIV, but the underlying mechanisms are poorly understood. Because IL-10 affects the phenotypic and functional properties of DCs, which are responsible for initiating adaptive immune responses, we investigated whether IL-10 induces changes in DC phenotype and function in the context of HIV infection. Here, we show that IL-10 treatment of immature and mature human DCs in culture induced contrasting phenotypic changes in these populations: immature DCs exhibited aberrant resistance to NK cell-mediated elimination, whereas mature DCs exhibited increased susceptibility to NKG2D-dependent NK elimination. Treatment of immature and mature DCs with HIV resulted in potent IL-10 secretion and the same phenotypic and functional changes observed in the IL-10-treated cells. Consistent with these in vitro data, LNs isolated from individuals infected with HIV exhibited aberrant accumulation of a partially "immature" DC population. Together, these data suggest that the progressive immune dysfunction observed in chronic viral infections might be caused in part by IL-10-induced reversal of DC susceptibility to NK cell-mediated elimination, resulting in the accumulation of poorly immunogenic DCs in LNs, the sites of adaptive immune response induction.
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Charlestown, Massachusetts 02129, USA. galter@partners.org
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
authors.forename: Daniel
authors.initials: D
authors.lastname: Kavanagh
authors.forename: Suzannah
authors.initials: S
authors.lastname: Rihn
authors.forename: Rutger
authors.initials: R
authors.lastname: Luteijn
authors.forename: David
authors.initials: D
authors.lastname: Brooks
authors.forename: Michael
authors.initials: M
authors.lastname: Oldstone
authors.forename: Jan
authors.initials: J
authors.lastname: van Lunzen
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
mesh_terms: D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000821:virology*; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology
chemical_list: D016753:Interleukin-10