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.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02097381.
authors.affiliation: Department of Public Health and Infectious Diseases, Istituto Pasteur - Fondazione Cenci-Bolognetti, University of Rome "Sapienza", Rome, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: d'Ettorre
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Baroncelli
authors.affiliation: Division of Microbiology and Immunology, Yerkes National Primate Research Center, Atlanta, Georgia, United States of America.
authors.forename: Luca
authors.initials: L
authors.lastname: Micci
authors.affiliation: Department of Public Health and Infectious Diseases, Istituto Pasteur - Fondazione Cenci-Bolognetti, University of Rome "Sapienza", Rome, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Ceccarelli
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Andreotti
authors.affiliation: Division of Pathology, Yerkes National Primate Research Center, Atlanta, Georgia, United States of America.
authors.forename: Prachi
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Department of Emergency Surgery- Emergency Endoscopic Unit, Policlinico Umberto I, University of Rome "Sapienza", Rome, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Fanello
authors.affiliation: Department of Emergency Surgery- Emergency Endoscopic Unit, Policlinico Umberto I, University of Rome "Sapienza", Rome, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Fiocca
authors.affiliation: Department of Public Health and Infectious Diseases, Istituto Pasteur - Fondazione Cenci-Bolognetti, University of Rome "Sapienza", Rome, Italy.
authors.forename: Eugenio Nelson
authors.initials: EN
authors.lastname: Cavallari
authors.affiliation: Department of Public Health and Infectious Diseases, Istituto Pasteur - Fondazione Cenci-Bolognetti, University of Rome "Sapienza", Rome, Italy.
authors.forename: Noemi
authors.initials: N
authors.lastname: Giustini
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mallano
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Clementina M
authors.initials: CM
authors.lastname: Galluzzo
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Vella
authors.affiliation: Infectious Disease Unit, Fondazione Eleonora Lorillard Spencer Cenci, Sapienza University, Latina, Italy.
authors.forename: Claudio M
authors.initials: CM
authors.lastname: Mastroianni
authors.affiliation: Division of Microbiology and Immunology, Yerkes National Primate Research Center, Atlanta, Georgia, United States of America; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.affiliation: Division of Microbiology and Immunology, Yerkes National Primate Research Center, Atlanta, Georgia, United States of America; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Mirko
authors.initials: M
authors.lastname: Paiardini
authors.affiliation: Department of Public Health and Infectious Diseases, Istituto Pasteur - Fondazione Cenci-Bolognetti, University of Rome "Sapienza", Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Vullo
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D007422:Intestines / Q000473:pathology*; D008070:Lipopolysaccharides / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D058504:Th17 Cells / Q000276:immunology*; D019562:Viral Load / Q000276:immunology
chemical_list: D020381:Interleukin-17; D008070:Lipopolysaccharides; D007371:Interferon-gamma