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

• Published in: European journal of immunology 2013-11, Vol.43 (11), p.2875-2885
• Main Authors: Clutton, Genevieve, Yang, Hongbing, Hancock, Gemma, Sande, Nellia, Holloway, Cameron, Angus, Brian, Delft, Annette, Barnes, Eleanor, Borrow, Persephone, Pellegrino, Pierre, Williams, Ian, McMichael, Andrew, Dorrell, Lucy
• Format: Article
• Language: English
• Subjects: Human immunodeficiency virus 1
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201343646

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) naive and 20 ART treated) showed that a subset of CD8 super(+) T cells with a CD25 super(neg) FoxP3 super(neg) phenotype contributes substantially to IL-10 production in response to HIV-1 gag stimulation. The frequencies of gag-specific IL-10- and IFN-[gamma]-producing T cells in ART-naive subjects were strongly correlated and the majority of these IL-10 super(+) CD8 super(+) T cells co-produced IFN-[gamma]; however, patients with a predominant IL-10 super(+)/IFN-[gamma] super(neg) profile showed better control of viraemia. Depletion of HIV-specific CD8 super(+) IL-10 super(+) cells from PBMCs led to upregulation of CD38 on CD14 super(+) 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 super(+) population and was also induced by exposure of monocytes to HIV-1 in vitro. Production of IL-10 by HIV-specific CD8 super(+) T cells may represent an adaptive regulatory response to monocyte activation during chronic infection.