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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.

Original publication

DOI

10.1002/eji.201343646

Type

Journal article

Journal

Eur J Immunol

Publication Date

11/2013

Volume

43

Pages

2875 - 2885

Keywords

CD8+ T cell, Cellular immunity, Immune activation, Interleukin-10 (IL-10), Monocyte, ADP-ribosyl Cyclase 1, Adult, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Female, Forkhead Transcription Factors, HIV Infections, HIV-1, Humans, Interferon-gamma, Interleukin-10, Interleukin-2 Receptor alpha Subunit, Interleukin-6, Lipopolysaccharide Receptors, Lymphocyte Activation, Male, Middle Aged, Up-Regulation, Viral Load, gag Gene Products, Human Immunodeficiency Virus