Chen, F

Goulder, P

Kang, Y

Klenerman, P

Luzzi, G

Prado, JG

Prendergast, A

Riddell, LA

English

PubMed

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BioMed Central
Page 1 of 1
(page number not for citation purposes)
Retrovirology
Open AccessOral presentation
OA031-01. HIV-1 infection is characterized by early loss of CD161+ 
Th17 cells and gradual decline in regulatory T cells
A Prendergast*1, JG Prado1, Y Kang1, F Chen2, LA Riddell3, G Luzzi4, 
P Goulder1 and P Klenerman1
Address: 1Department of Paediatrics, University of Oxford, Oxford, UK, 2Royal Berkshire NHS Foundation Trust, Reading, UK, 3Northampton 
General Hospital, Northampton, UK and 4Wycombe Hospital, High Wycombe, UK
* Corresponding author    
Background
CD4 cell depletion is central to HIV pathogenesis. How-
ever, CD4 cells present diverse lineages and the relative
impact of HIV on Th17 and regulatory T cell (Treg) subsets
remains unclear. CD161+ CD4 cells are a recently identi-
fied, gut-homing population with Th17 precursor poten-
tial. The balance between pro-inflammatory Th17 cells
and immunoregulatory Tregs may be critical in HIV
pathogenesis. This study addressed changes in CD161+,
Th17 and Treg subsets during untreated HIV infection.
Methods
Peripheral blood mononuclear cells (PBMC) were iso-
lated from 77 untreated HIV-infected and 36 HIV-unin-
fected subjects and stained with fluorochrome-conjugated
monoclonal antibodies to characterize CD161+ CD4
cells; Th17 cells (expression of CCR6 and elaboration of
IL-17A after PMA/ionomycin stimulation); Tregs
(CD4+CD25hiFoxP3+ cells); and CD8 activation
(CD38+/HLA-DR+ cells). In vitro infectability of CD161+
and Th17 cells was assessed by incubating activated
healthy donor CD4 cells with HIV Bal for 5 days and co-
staining for CD161/IL-17A and intracellular p24.
Results
Peripheral blood Th17 cells were depleted 10-fold in HIV-
infected, compared to HIV-uninfected, subjects (P <
0.0001) across a range of disease stages, accompanied by
a significant reduction of CD161+ T cells (P = 0.024).
Both Th17 cells and CD161+ CD4 cells were highly tar-
geted by HIV in vitro. The preferential and early loss of
Th17 cells contrasted with a gradual decline in absolute
Treg numbers during HIV disease progression in untreated
subjects followed longitudinally (R = 0.71, P = 0.003).
Loss of Tregs was associated with increased immune acti-
vation (R = -0.33, P = 0.03).
Conclusion
HIV-infected subjects showed preferential loss of Th17
and CD161+ CD4 subsets, which were both highly tar-
geted by HIV in vitro. Loss of CD161+ cells, which are
Th17 cell precursors, may limit Th17 reconstitution. A
gradual decline in Tregs during disease progression was
associated with increased immune activation. Loss of
both Th17 and Treg subsets may enhance disease progres-
sion through impaired mucosal defences, and increase in
immune activation.
from AIDS Vaccine 2009
Paris, France. 19–22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):O19 doi:10.1186/1742-4690-6-S3-O19
<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>
This abstract is available from: http://www.retrovirology.com/content/6/S3/O19
© 2009 Prendergast et al; licensee BioMed Central Ltd. 


OA031-01. HIV-1 infection is characterized by early loss of CD161+ Th17 cells and gradual decline in regulatory T cells

A Prendergast

JG Prado

Y Kang

F Chen

LA Riddell

G Luzzi

P Goulder

P Klenerman

Crossref

BioMed CentralPage 1 of 1(page number not for citation purposes)RetrovirologyOpen AccessOral presentationOA031-01. HIV-1 infection is characterized by early loss of CD161+ Th17 cells and gradual decline in regulatory T cellsA Prendergast*1, JG Prado1, Y Kang1, F Chen2, LA Riddell3, G Luzzi4, P Goulder1 and P Klenerman1Address: 1Department of Paediatrics, University of Oxford, Oxford, UK, 2Royal Berkshire NHS Foundation Trust, Reading, UK, 3Northampton General Hospital, Northampton, UK and 4Wycombe Hospital, High Wycombe, UK* Corresponding author    BackgroundCD4 cell depletion is central to HIV pathogenesis. How-ever, CD4 cells present diverse lineages and the relativeimpact of HIV on Th17 and regulatory T cell (Treg) subsetsremains unclear. CD161+ CD4 cells are a recently identi-fied, gut-homing population with Th17 precursor poten-tial. The balance between pro-inflammatory Th17 cellsand immunoregulatory Tregs may be critical in HIVpathogenesis. This study addressed changes in CD161+,Th17 and Treg subsets during untreated HIV infection.MethodsPeripheral blood mononuclear cells (PBMC) were iso-lated from 77 untreated HIV-infected and 36 HIV-unin-fected subjects and stained with fluorochrome-conjugatedmonoclonal antibodies to characterize CD161+ CD4cells; Th17 cells (expression of CCR6 and elaboration ofIL-17A after PMA/ionomycin stimulation); Tregs(CD4+CD25hiFoxP3+ cells); and CD8 activation(CD38+/HLA-DR+ cells). In vitro infectability of CD161+and Th17 cells was assessed by incubating activatedhealthy donor CD4 cells with HIV Bal for 5 days and co-staining for CD161/IL-17A and intracellular p24.ResultsPeripheral blood Th17 cells were depleted 10-fold in HIV-infected, compared to HIV-uninfected, subjects (P <0.0001) across a range of disease stages, accompanied bya significant reduction of CD161+ T cells (P = 0.024).Both Th17 cells and CD161+ CD4 cells were highly tar-geted by HIV in vitro. The preferential and early loss ofTh17 cells contrasted with a gradual decline in absoluteTreg numbers during HIV disease progression in untreatedsubjects followed longitudinally (R = 0.71, P = 0.003).Loss of Tregs was associated with increased immune acti-vation (R = -0.33, P = 0.03).ConclusionHIV-infected subjects showed preferential loss of Th17and CD161+ CD4 subsets, which were both highly tar-geted by HIV in vitro. Loss of CD161+ cells, which areTh17 cell precursors, may limit Th17 reconstitution. Agradual decline in Tregs during disease progression wasassociated with increased immune activation. Loss ofboth Th17 and Treg subsets may enhance disease progres-sion through impaired mucosal defences, and increase inimmune activation.from AIDS Vaccine 2009Paris, France. 19–22 October 2009Published: 22 October 2009Retrovirology 2009, 6(Suppl 3):O19 doi:10.1186/1742-4690-6-S3-O19<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>This abstract is available from: http://www.retrovirology.com/content/6/S3/O19© 2009 Prendergast et al; licensee BioMed Central Ltd. 

Goulder P

Luzzi G

Riddell LA

Chen F

Kang Y

Prado JG

Prendergast A

Klenerman P

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OA031-01. HIV-1 infection is characterized by early loss of CD161+ Th17 cells and gradual decline in regulatory T cells

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