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

Abstract:

: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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Brezar V,Ruffin N,Richert L,Surenaud M,Lacabaratz C,Palucka K,Thiébaut R,Banchereau J,Levy Y,Seddiki N

doi

10.1371/journal.ppat.1004752

subject

Has Abstract

pub_date

2015-03-27 00:00:00

pages

e1004752

issue

3

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-14-02524

journal_volume

11

pub_type

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