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

• Published in: PloS one Vol. 9; no. 10; p. e109791
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23-10-2014; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Antiretroviral Therapy, Highly Active; Biology and Life Sciences; Blood; CD14 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; Cell activation; Cell Proliferation; Chronic illnesses; Clinical trials; Cytometry; Digestive system; Digestive tract; Drug therapy; Endoscopy; Enzyme-linked immunosorbent assay; Gastrointestinal tract; Gene expression; Health aspects; Helper cells; HIV; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; Human immunodeficiency virus; Humans; Immune system; Immunohistochemistry; Immunology; Infection; Infections; Infectious diseases; Inflammation; Interferon-gamma - biosynthesis; Interleukin-17 - biosynthesis; Intestine; Intestines - pathology; Laboratories; Lipopolysaccharides; Lipopolysaccharides - blood; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Male; Markers; Medicine; Medicine and health sciences; Microorganisms; Middle Aged; Mucosa; Pathology; Pretreatment; Public health; rRNA 16S; Studies; T cells; Th17 Cells - immunology; Therapy; Translocation; Viral Load - immunology; Atlanta Georgia; Italy; Georgia; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0109791

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.
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.
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.
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.
ClinicalTrials.gov NCT02097381.