PD-1 expression and cytokine secretion profiles of Mycobacterium tuberculosis-specific CD4+ T-cell subsets; potential correlates of containment in HIV-TB co-infection
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
HIV co-infection is an important risk factor for tuberculosis (TB) providing a powerful model in which to dissect out defective, protective and dysfunctional Mycobacterium tuberculosis (MTB)-specific immune responses. To identify the changes induced by HIV co-infection we compared MTB-specific CD4+ responses in subjects with active TB and latent TB infection (LTBI), with and without HIV co-infection. CD4+ T-cell subsets producing interferon-gamma (IFN-γ), interleukin-2 (IL-2) and tumour necrosis factor-alpha (TNF-α) and expressing CD279 (PD-1) were measured using polychromatic flow-cytometry. HIV-TB co-infection was consistently and independently associated with a reduced frequency of CD4+ IFN-γ and IL-2-dual secreting T-cells and the proportion correlated inversely with HIV viral load (VL). The impact of HIV co-infection on this key MTB-specific T-cell subset identifies them as a potential correlate of mycobacterial immune containment. The percentage of MTB-specific IFN-γ-secreting T-cell subsets that expressed PD-1 was increased in active TB with HIV co-infection and correlated with VL. This identifies a novel correlate of dysregulated immunity to MTB, which may in part explain the paucity of inflammatory response in the face of mycobacterial dissemination that characterizes active TB with HIV co-infection.
Date Issued
2016-01-12
Date Acceptance
2015-12-31
Citation
PLOS One, 2016, 11 (1)
ISSN
1932-6203
Publisher
Public Library of Science
Journal / Book Title
PLOS One
Volume
11
Issue
1
Copyright Statement
© 2016 Pollock et al. 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
credited.
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
credited.
License URL
Sponsor
Wellcome Trust
Grant Number
RG51553
Subjects
General Science & Technology
MD Multidisciplinary
Publication Status
Published
Article Number
e0146905