Journal Article

PD-1 Expression and Cytokine Secretion Profiles of Mycobacterium tuberculosis-Specific CD4+ T-Cell Subsets; Potential Correlates of Containment in HIV-TB Co-Infection

Pollock, Katrina M., Cooke, Graham S., Grass, Lisa, Lalvani, Ajit, Kapembwa, Moses S., Montamat-Sicotte, Damien J., Taylor, Graham P., Kon, Onn M., Sampson, Robert D.

2016

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acquired immune deficiency syndrome / Adult / AIDS / Antigens / Antigens, Bacterial - metabolism / Antiretroviral drugs / Biological response modifiers / Care and treatment / CD4 antigen / CD4-Positive T-Lymphocytes - cytology / CD4-Positive T-Lymphocytes - microbiology / Coinfection - microbiology / Coinfection - virology / Committees / Containment / Correlation / Cytokines / Cytometry / Diagnosis / Ethics / Female / Flow cytometry / Gene Expression Regulation / Genotype & phenotype / Health aspects / Health risks / Heart / HIV / HIV Infections - blood / HIV Infections - complications / Human immunodeficiency virus / Humans / Immune response / Immunity / Immunology / Immunophenotyping / Infections / Inflammation / Inflammatory response / Interferon / Interferon-gamma - metabolism / Interleukin 2 / Interleukin-2 - metabolism / Latent Tuberculosis - blood / Latent Tuberculosis - complications / Lymphocyte Subsets - microbiology / Lymphocytes / Lymphocytes T / Male / Middle Aged / Mortality / Mycobacterium tuberculosis / PD-1 protein / Programmed Cell Death 1 Receptor - metabolism / Risk factors / T cell receptors / Tuberculosis / Tuberculosis - blood / Tuberculosis - complications / Tumor necrosis factor / Tumor Necrosis Factor-alpha - metabolism / Tumor necrosis factor-α / Tumors / Virology / Young Adult / γ-Interferon