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

作者：Clutton Genevieve; Yang Hongbing; Hancock Gemma; Sande Nellia; Holloway Cameron; Angus Brian; von Delft Annette; Barnes Eleanor; Borrow Persephone; Pellegrino Pierre; Williams Ian; McMichael Andrew; Dorrell Lucy^*

来源：European Journal of Immunology, 2013, 43(11): 2875-2885.

DOI：10.1002/eji.201343646

• CD8(+) T cell
• Cellular immunity
• Immune activation
• Interleukin-10 (IL-10)
• Monocyte

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(+) 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-gamma-producing T cells in ART-naive subjects were strongly correlated and the majority of these IL-10(+) CD8(+) T cells co-produced IFN-gamma; however, patients with a predominant IL-10(+)/IFN-gamma-(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.

• 出版日期2013-11