Published in

Public Library of Science, PLoS ONE, 10(9), p. e109791, 2014

DOI: 10.1371/journal.pone.0109791

Links

Tools

Export citation

Search in Google Scholar

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

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Green circle
Preprint: archiving allowed
Green circle
Postprint: archiving allowed
Green circle
Published version: archiving allowed
Data provided by SHERPA/RoMEO

Abstract

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 naive 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.