CD4 T-cell responses in primary HIV infection: interrelationship with immune activation and virus burden
Early events during primary HIV infection (PHI) are thought to influence disease outcome. Although a growing body of evidence suggests a beneficial role of HIV-specific CD4 help in HIV infection, it is unclear how early viral replication, systemic immune activation and antiretroviral therapy (ART) m...
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doaj-cbc6719b889e482aa9eef7e9d423fde02020-11-24T21:04:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242016-09-01710.3389/fimmu.2016.00395216178CD4 T-cell responses in primary HIV infection: interrelationship with immune activation and virus burdenMathieu F. Chevalier0Mathieu F. Chevalier1Mathieu F. Chevalier2Céline Didier3Pierre-Marie Girard4Maria E Manea5Pauline Campa6Françoise Barré-Sinoussi7Daniel Scott-Algara8Laurence Weiss9Laurence Weiss10Laurence Weiss11Institut PasteurSorbonne Paris CitéLausanne University HospitalInstitut PasteurAP-HPAP-HPAP-HPInstitut PasteurInstitut PasteurInstitut PasteurAP-HPSorbonne Paris CitéEarly events during primary HIV infection (PHI) are thought to influence disease outcome. Although a growing body of evidence suggests a beneficial role of HIV-specific CD4 help in HIV infection, it is unclear how early viral replication, systemic immune activation and antiretroviral therapy (ART) may shape CD4 T-cell responses during PHI, and whether HIV-specific CD4 responses contribute to the high immune activation observed in PHI. Twenty-seven patients with early PHI were included in a prospective longitudinal study and twelve of them received ART after enrollment. Fresh PBMC were used for measurement of ex-vivo T-cell activation and of cytokine-producing CD4 T-cells following stimulation with PMA/ionomycin or HIV-1-gag-p24 antigen. Patients were segregated based on CD8 T-cell activation level (i.e. %HLA-DR+CD38+ CD8 T-cells) at baseline. Patients with lower immune activation exhibited higher frequency of bulk CD4 T-cells producing IFN-γ or IL-17, and higher effector-to-regulatory cell ratios. No differences were found in HIV-specific CD4 T-cell frequencies. In contrast, segregation of patients based on plasma-viral load (pVL) revealed that patients with higher pVL showed higher cytokine-producing HIV-specific CD4 responses. Of note, the frequency of IFN-γ+ HIV-specific CD4 T cells significantly diminished between baseline and month-6 only in ART-treated patients. However, early treatment initiation was associated with better maintenance of HIV-specific IFN-γ+ CD4 T-cells. These data suggest that HIV-specific CD4 responses do not fuel systemic T-cell activation, and are driven by viral replication but not able to contribute to its control in the early phase of infection. Moreover, our data also suggest a benefit of early treatment for the maintenance of HIV-specific CD4 T-cell help.http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00395/fullViral LoadHIV-specific CD4 T cellsantiretroviral therapyacute HIV infectiongeneralized immune activationearly ART initiation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mathieu F. Chevalier Mathieu F. Chevalier Mathieu F. Chevalier Céline Didier Pierre-Marie Girard Maria E Manea Pauline Campa Françoise Barré-Sinoussi Daniel Scott-Algara Laurence Weiss Laurence Weiss Laurence Weiss |
spellingShingle |
Mathieu F. Chevalier Mathieu F. Chevalier Mathieu F. Chevalier Céline Didier Pierre-Marie Girard Maria E Manea Pauline Campa Françoise Barré-Sinoussi Daniel Scott-Algara Laurence Weiss Laurence Weiss Laurence Weiss CD4 T-cell responses in primary HIV infection: interrelationship with immune activation and virus burden Frontiers in Immunology Viral Load HIV-specific CD4 T cells antiretroviral therapy acute HIV infection generalized immune activation early ART initiation |
author_facet |
Mathieu F. Chevalier Mathieu F. Chevalier Mathieu F. Chevalier Céline Didier Pierre-Marie Girard Maria E Manea Pauline Campa Françoise Barré-Sinoussi Daniel Scott-Algara Laurence Weiss Laurence Weiss Laurence Weiss |
author_sort |
Mathieu F. Chevalier |
title |
CD4 T-cell responses in primary HIV infection: interrelationship with immune activation and virus burden |
title_short |
CD4 T-cell responses in primary HIV infection: interrelationship with immune activation and virus burden |
title_full |
CD4 T-cell responses in primary HIV infection: interrelationship with immune activation and virus burden |
title_fullStr |
CD4 T-cell responses in primary HIV infection: interrelationship with immune activation and virus burden |
title_full_unstemmed |
CD4 T-cell responses in primary HIV infection: interrelationship with immune activation and virus burden |
title_sort |
cd4 t-cell responses in primary hiv infection: interrelationship with immune activation and virus burden |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2016-09-01 |
description |
Early events during primary HIV infection (PHI) are thought to influence disease outcome. Although a growing body of evidence suggests a beneficial role of HIV-specific CD4 help in HIV infection, it is unclear how early viral replication, systemic immune activation and antiretroviral therapy (ART) may shape CD4 T-cell responses during PHI, and whether HIV-specific CD4 responses contribute to the high immune activation observed in PHI. Twenty-seven patients with early PHI were included in a prospective longitudinal study and twelve of them received ART after enrollment. Fresh PBMC were used for measurement of ex-vivo T-cell activation and of cytokine-producing CD4 T-cells following stimulation with PMA/ionomycin or HIV-1-gag-p24 antigen. Patients were segregated based on CD8 T-cell activation level (i.e. %HLA-DR+CD38+ CD8 T-cells) at baseline. Patients with lower immune activation exhibited higher frequency of bulk CD4 T-cells producing IFN-γ or IL-17, and higher effector-to-regulatory cell ratios. No differences were found in HIV-specific CD4 T-cell frequencies. In contrast, segregation of patients based on plasma-viral load (pVL) revealed that patients with higher pVL showed higher cytokine-producing HIV-specific CD4 responses. Of note, the frequency of IFN-γ+ HIV-specific CD4 T cells significantly diminished between baseline and month-6 only in ART-treated patients. However, early treatment initiation was associated with better maintenance of HIV-specific IFN-γ+ CD4 T-cells. These data suggest that HIV-specific CD4 responses do not fuel systemic T-cell activation, and are driven by viral replication but not able to contribute to its control in the early phase of infection. Moreover, our data also suggest a benefit of early treatment for the maintenance of HIV-specific CD4 T-cell help. |
topic |
Viral Load HIV-specific CD4 T cells antiretroviral therapy acute HIV infection generalized immune activation early ART initiation |
url |
http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00395/full |
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