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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.

Original publication

DOI

10.1371/journal.pone.0146905

Type

Journal article

Journal

PLoS One

Publication Date

2016

Volume

11

Keywords

Adult, Antigens, Bacterial, CD4-Positive T-Lymphocytes, Coinfection, Female, Gene Expression Regulation, HIV Infections, Humans, Immunophenotyping, Interferon-gamma, Interleukin-2, Latent Tuberculosis, Lymphocyte Subsets, Male, Middle Aged, Mycobacterium tuberculosis, Programmed Cell Death 1 Receptor, Tuberculosis, Tumor Necrosis Factor-alpha, Young Adult