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Reconstitution of Intestinal CD4 and Th17 T Cells in Antiretroviral Therapy Suppressed HIV-Infected Subjects: Implication for Residual Immune Activation from the Results of a Clinical Trial

INTRODUCTION: During HIV infection the severe depletion of intestinal CD4(+) T-cells is associated with microbial translocation, systemic immune activation, and disease progression. This study examined intestinal and peripheral CD4(+) T-cell subsets reconstitution under combined antiretroviral thera...

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Autores principales: d'Ettorre, Gabriella, Baroncelli, Silvia, Micci, Luca, Ceccarelli, Giancarlo, Andreotti, Mauro, Sharma, Prachi, Fanello, Gianfranco, Fiocca, Fausto, Cavallari, Eugenio Nelson, Giustini, Noemi, Mallano, Alessandra, Galluzzo, Clementina M., Vella, Stefano, Mastroianni, Claudio M., Silvestri, Guido, Paiardini, Mirko, Vullo, Vincenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207675/
https://www.ncbi.nlm.nih.gov/pubmed/25340778
http://dx.doi.org/10.1371/journal.pone.0109791
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author d'Ettorre, Gabriella
Baroncelli, Silvia
Micci, Luca
Ceccarelli, Giancarlo
Andreotti, Mauro
Sharma, Prachi
Fanello, Gianfranco
Fiocca, Fausto
Cavallari, Eugenio Nelson
Giustini, Noemi
Mallano, Alessandra
Galluzzo, Clementina M.
Vella, Stefano
Mastroianni, Claudio M.
Silvestri, Guido
Paiardini, Mirko
Vullo, Vincenzo
author_facet d'Ettorre, Gabriella
Baroncelli, Silvia
Micci, Luca
Ceccarelli, Giancarlo
Andreotti, Mauro
Sharma, Prachi
Fanello, Gianfranco
Fiocca, Fausto
Cavallari, Eugenio Nelson
Giustini, Noemi
Mallano, Alessandra
Galluzzo, Clementina M.
Vella, Stefano
Mastroianni, Claudio M.
Silvestri, Guido
Paiardini, Mirko
Vullo, Vincenzo
author_sort d'Ettorre, Gabriella
collection PubMed
description INTRODUCTION: During HIV infection the severe depletion of intestinal CD4(+) T-cells is associated with microbial translocation, systemic immune activation, and disease progression. This study examined intestinal and peripheral CD4(+) T-cell subsets reconstitution under combined antiretroviral therapy (cART), and systemic immune activation markers. METHODS: This longitudinal single-arm pilot study evaluates CD4(+) T cells, including Th1 and Th17, in gut and blood and soluble markers for inflammation in HIV-infected individuals before (M0) and after eight (M8) months of cART. From January 2010 to December 2011, 10 HIV-1 naïve patients were screened and 9 enrolled. Blood and gut CD4(+) T-cells subsets and cellular immune activation were determined by flow-cytometry and plasma soluble CD14 by ELISA. CD4(+) Th17 cells were detected in gut biopsies by immunohistochemistry. Microbial translocation was measured by limulus-amebocyte-lysate assay to detect bacterial lipopolysaccharide (LPS) and PCR Real Time to detect plasma bacterial 16S rDNA. RESULTS: Eight months of cART increased intestinal CD4(+) and Th17 cells and reduced levels of T-cell activation and proliferation. The magnitude of intestinal CD4(+) T-cell reconstitution correlated with the reduction of plasma LPS. Importantly, the magnitude of Th17 cells reconstitution correlated directly with blood CD4(+) T-cell recovery. CONCLUSION: Short-term antiretroviral therapy resulted in a significant increase in the levels of total and Th17 CD4(+) T-cells in the gut mucosa and in decline of T-cell activation. The observation that pre-treatment levels of CD4(+) and of CD8(+) T-cell activation are predictors of the magnitude of Th17 cell reconstitution following cART provides further rationale for an early initiation of cART in HIV-infected individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT02097381
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spelling pubmed-42076752014-10-27 Reconstitution of Intestinal CD4 and Th17 T Cells in Antiretroviral Therapy Suppressed HIV-Infected Subjects: Implication for Residual Immune Activation from the Results of a Clinical Trial d'Ettorre, Gabriella Baroncelli, Silvia Micci, Luca Ceccarelli, Giancarlo Andreotti, Mauro Sharma, Prachi Fanello, Gianfranco Fiocca, Fausto Cavallari, Eugenio Nelson Giustini, Noemi Mallano, Alessandra Galluzzo, Clementina M. Vella, Stefano Mastroianni, Claudio M. Silvestri, Guido Paiardini, Mirko Vullo, Vincenzo PLoS One Research Article INTRODUCTION: During HIV infection the severe depletion of intestinal CD4(+) T-cells is associated with microbial translocation, systemic immune activation, and disease progression. This study examined intestinal and peripheral CD4(+) T-cell subsets reconstitution under combined antiretroviral therapy (cART), and systemic immune activation markers. METHODS: This longitudinal single-arm pilot study evaluates CD4(+) T cells, including Th1 and Th17, in gut and blood and soluble markers for inflammation in HIV-infected individuals before (M0) and after eight (M8) months of cART. From January 2010 to December 2011, 10 HIV-1 naïve patients were screened and 9 enrolled. Blood and gut CD4(+) T-cells subsets and cellular immune activation were determined by flow-cytometry and plasma soluble CD14 by ELISA. CD4(+) Th17 cells were detected in gut biopsies by immunohistochemistry. Microbial translocation was measured by limulus-amebocyte-lysate assay to detect bacterial lipopolysaccharide (LPS) and PCR Real Time to detect plasma bacterial 16S rDNA. RESULTS: Eight months of cART increased intestinal CD4(+) and Th17 cells and reduced levels of T-cell activation and proliferation. The magnitude of intestinal CD4(+) T-cell reconstitution correlated with the reduction of plasma LPS. Importantly, the magnitude of Th17 cells reconstitution correlated directly with blood CD4(+) T-cell recovery. CONCLUSION: Short-term antiretroviral therapy resulted in a significant increase in the levels of total and Th17 CD4(+) T-cells in the gut mucosa and in decline of T-cell activation. The observation that pre-treatment levels of CD4(+) and of CD8(+) T-cell activation are predictors of the magnitude of Th17 cell reconstitution following cART provides further rationale for an early initiation of cART in HIV-infected individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT02097381 Public Library of Science 2014-10-23 /pmc/articles/PMC4207675/ /pubmed/25340778 http://dx.doi.org/10.1371/journal.pone.0109791 Text en © 2014 d'Ettorre et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
d'Ettorre, Gabriella
Baroncelli, Silvia
Micci, Luca
Ceccarelli, Giancarlo
Andreotti, Mauro
Sharma, Prachi
Fanello, Gianfranco
Fiocca, Fausto
Cavallari, Eugenio Nelson
Giustini, Noemi
Mallano, Alessandra
Galluzzo, Clementina M.
Vella, Stefano
Mastroianni, Claudio M.
Silvestri, Guido
Paiardini, Mirko
Vullo, Vincenzo
Reconstitution of Intestinal CD4 and Th17 T Cells in Antiretroviral Therapy Suppressed HIV-Infected Subjects: Implication for Residual Immune Activation from the Results of a Clinical Trial
title Reconstitution of Intestinal CD4 and Th17 T Cells in Antiretroviral Therapy Suppressed HIV-Infected Subjects: Implication for Residual Immune Activation from the Results of a Clinical Trial
title_full Reconstitution of Intestinal CD4 and Th17 T Cells in Antiretroviral Therapy Suppressed HIV-Infected Subjects: Implication for Residual Immune Activation from the Results of a Clinical Trial
title_fullStr Reconstitution of Intestinal CD4 and Th17 T Cells in Antiretroviral Therapy Suppressed HIV-Infected Subjects: Implication for Residual Immune Activation from the Results of a Clinical Trial
title_full_unstemmed Reconstitution of Intestinal CD4 and Th17 T Cells in Antiretroviral Therapy Suppressed HIV-Infected Subjects: Implication for Residual Immune Activation from the Results of a Clinical Trial
title_short Reconstitution of Intestinal CD4 and Th17 T Cells in Antiretroviral Therapy Suppressed HIV-Infected Subjects: Implication for Residual Immune Activation from the Results of a Clinical Trial
title_sort reconstitution of intestinal cd4 and th17 t cells in antiretroviral therapy suppressed hiv-infected subjects: implication for residual immune activation from the results of a clinical trial
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207675/
https://www.ncbi.nlm.nih.gov/pubmed/25340778
http://dx.doi.org/10.1371/journal.pone.0109791
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