Emergence of a distinct HIV-specific IL-10-producing CD8+ T-cell subset with immunomodulatory functions during chronic HIV-1 infection.

Journal article

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: Clutton, G; Yang, H; Hancock, G; Sande, N; Holloway, C

• Publication status: Published
• Journal: European journal of immunology
• Volume: 43
• Issue: 11
• Pages: 2875-2885
• Publication date: 2013-11-01
• DOI: 10.1002/eji.201343646
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: gag Gene Products, Human Immunodeficiency Virus; Male; Forkhead Transcription Factors; Middle Aged; HIV Infections; Interleukin-2 Receptor alpha Subunit; Up-Regulation; Lymphocyte Activation; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Viral Load; CD8-Positive T-Lymphocytes; CD4-Positive T-Lymphocytes; Antigens, CD38; Female; Humans; Interleukin-10; Interleukin-6; HIV-1; Antigens, CD14; Interferon-gamma; Adult