title: Emergence of a distinct HIV-specific IL-10-producing CD8+ T-cell subset with immunomodulatory functions during chronic HIV-1 infection.
abstract: Interleukin-10 (IL-10) plays a key role in regulating proinflammatory immune responses to infection but can interfere with pathogen clearance. Although IL-10 is upregulated throughout HIV-1 infection in multiple cell subsets, whether this is a viral immune evasion strategy or an appropriate response to immune activation is unresolved. Analysis of IL-10 production at the single cell level in 51 chronically infected subjects (31 antiretroviral (ART) naïve and 20 ART treated) showed that a subset of CD8(+) T cells with a CD25(neg) FoxP3(neg) phenotype contributes substantially to IL-10 production in response to HIV-1 gag stimulation. The frequencies of gag-specific IL-10- and IFN-γ-producing T cells in ART-naïve subjects were strongly correlated and the majority of these IL-10(+) CD8(+) T cells co-produced IFN-γ; however, patients with a predominant IL-10(+) /IFN-γ(neg) profile showed better control of viraemia. Depletion of HIV-specific CD8(+) IL-10(+) cells from PBMCs led to upregulation of CD38 on CD14(+) monocytes together with increased IL-6 production, in response to gag stimulation. Increased CD38 expression was positively correlated with the frequency of the IL-10(+) population and was also induced by exposure of monocytes to HIV-1 in vitro. Production of IL-10 by HIV-specific CD8(+) T cells may represent an adaptive regulatory response to monocyte activation during chronic infection.
authors.affiliation: Oxford NIHR Biomedical Research Centre, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Clutton
authors.forename: Hongbing
authors.initials: H
authors.lastname: Yang
authors.forename: Gemma
authors.initials: G
authors.lastname: Hancock
authors.forename: Nellia
authors.initials: N
authors.lastname: Sande
authors.forename: Cameron
authors.initials: C
authors.lastname: Holloway
authors.forename: Brian
authors.initials: B
authors.lastname: Angus
authors.forename: Annette
authors.initials: A
authors.lastname: von Delft
authors.forename: Eleanor
authors.initials: E
authors.lastname: Barnes
authors.forename: Persephone
authors.initials: P
authors.lastname: Borrow
authors.forename: Pierre
authors.initials: P
authors.lastname: Pellegrino
authors.forename: Ian
authors.initials: I
authors.lastname: Williams
authors.forename: Andrew
authors.initials: A
authors.lastname: McMichael
authors.forename: Lucy
authors.initials: L
authors.lastname: Dorrell
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D054301:gag Gene Products, Human Immunodeficiency Virus; D016753:Interleukin-10; D007371:Interferon-gamma; D051997:ADP-ribosyl Cyclase 1
keywords: CD8+ T cell; Cellular immunity; Immune activation; Interleukin-10 (IL-10); Monocyte