Decreased HIV-specific T-regulatory responses are associated with effective DC-vaccine induced immunity

The role of regulatory T cells (Tregs) in vaccination has been poorly investigated. We have reported that vaccination with ex vivo-generated dendritic-cells (DC) loaded with HIV-lipopeptides (LIPO-5-DC vaccine) in HIV-infected patients was well tolerated and highly immunogenic. These responses and t...

Full description

Saved in:
Bibliographic Details
Published in:PLoS pathogens 2015-03, Vol.11 (3), p.e1004752-e1004752
Main Authors: Brezar, Vedran, Ruffin, Nicolas, Richert, Laura, Surenaud, Mathieu, Lacabaratz, Christine, Palucka, Karolina, Thiébaut, Rodolphe, Banchereau, Jacques, Levy, Yves, Seddiki, Nabila
Format: Article
Language:English
Subjects:
Adult
AIDS vaccines
AIDS Vaccines - administration & dosage
AIDS Vaccines - immunology
Antigens
Antiretroviral drugs
Clinical trials
Complications and side effects
Cytokines
Dendritic Cells - immunology
Drug therapy
Female
Genetic aspects
Health aspects
HIV
HIV-1 - immunology
Host-virus relationships
Human immunodeficiency virus
Humans
Identification and classification
Interferon-gamma - immunology
Life Sciences
Lymphocytes
Male
Middle Aged
Santé publique et épidémiologie
T cell receptors
T cells
T-Lymphocytes, Regulatory - immunology
Viral Load
Virus replication
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The role of regulatory T cells (Tregs) in vaccination has been poorly investigated. We have reported that vaccination with ex vivo-generated dendritic-cells (DC) loaded with HIV-lipopeptides (LIPO-5-DC vaccine) in HIV-infected patients was well tolerated and highly immunogenic. These responses and their relation to viral replication following analytical treatment interruption (ATI) were variable. Here, we investigated whether the presence of HIV-specific Tregs might explain these differences. Co-expression of CD25, CD134, CD39 and FoxP3 was used to delineate both antigen-specific Tregs and effectors T cells (Teffs). Median LIPO-5 specific-CD25+CD134+ polyfunctional T cells increased from 0.1% (IQR 0-0.3) before vaccination (week -4) to 2.1% (IQR 1.1-3.9) at week 16 following 4 immunizations (p=0.001) and were inversely correlated with maximum viral load following ATI (r=-0.77, p=0.001). Vaccinees who displayed lower levels of HIV-specific CD4+CD134+CD25+CD39+FoxP3+ Tregs responded better to the LIPO-5-DC vaccine. After vaccination, the frequency of HIV-specific Tregs decreased (from 69.3 at week -4 to 31.7% at week 16) and inversely correlated with HIV-specific IFN-γ-producing cells (r=-0.64, p=0.002). We show that therapeutic immunization skewed the HIV-specific response from regulatory to effector phenotype which impacts on the magnitude of viral replication following ATI.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1004752