Emergence of a distinct HIV-specific IL-10-producing CD8+ T-cell subset with immunomodulatory functions during chronic HIV-1 infection.
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2013
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| _version_ | 1797063347449888768 |
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| author | Clutton, G Yang, H Hancock, G Sande, N Holloway, C Angus, B von Delft, A Barnes, E Borrow, P Pellegrino, P Williams, I McMichael, A Dorrell, L |
| author_facet | Clutton, G Yang, H Hancock, G Sande, N Holloway, C Angus, B von Delft, A Barnes, E Borrow, P Pellegrino, P Williams, I McMichael, A Dorrell, L |
| author_sort | Clutton, G |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T20:58:32Z |
| format | Journal article |
| id | oxford-uuid:3a15920e-5a7b-44de-9f48-fdcfffb2cabc |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:58:32Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:3a15920e-5a7b-44de-9f48-fdcfffb2cabc2022-03-26T13:59:27ZEmergence of a distinct HIV-specific IL-10-producing CD8+ T-cell subset with immunomodulatory functions during chronic HIV-1 infection.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3a15920e-5a7b-44de-9f48-fdcfffb2cabcEnglishSymplectic Elements at Oxford2013Clutton, GYang, HHancock, GSande, NHolloway, CAngus, Bvon Delft, ABarnes, EBorrow, PPellegrino, PWilliams, IMcMichael, ADorrell, LInterleukin-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. |
| spellingShingle | Clutton, G Yang, H Hancock, G Sande, N Holloway, C Angus, B von Delft, A Barnes, E Borrow, P Pellegrino, P Williams, I McMichael, A Dorrell, L Emergence of a distinct HIV-specific IL-10-producing CD8+ T-cell subset with immunomodulatory functions during chronic HIV-1 infection. |
| title | Emergence of a distinct HIV-specific IL-10-producing CD8+ T-cell subset with immunomodulatory functions during chronic HIV-1 infection. |
| title_full | Emergence of a distinct HIV-specific IL-10-producing CD8+ T-cell subset with immunomodulatory functions during chronic HIV-1 infection. |
| title_fullStr | Emergence of a distinct HIV-specific IL-10-producing CD8+ T-cell subset with immunomodulatory functions during chronic HIV-1 infection. |
| title_full_unstemmed | Emergence of a distinct HIV-specific IL-10-producing CD8+ T-cell subset with immunomodulatory functions during chronic HIV-1 infection. |
| title_short | Emergence of a distinct HIV-specific IL-10-producing CD8+ T-cell subset with immunomodulatory functions during chronic HIV-1 infection. |
| title_sort | emergence of a distinct hiv specific il 10 producing cd8 t cell subset with immunomodulatory functions during chronic hiv 1 infection |
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