title: PD-1 Expression and Cytokine Secretion Profiles of Mycobacterium tuberculosis-Specific CD4+ T-Cell Subsets; Potential Correlates of Containment in HIV-TB Co-Infection.
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.
authors.affiliation: Tuberculosis Research Centre, Respiratory Infections Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Pollock
authors.affiliation: Tuberculosis Research Centre, Respiratory Infections Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Damien J
authors.initials: DJ
authors.lastname: Montamat-Sicotte
authors.affiliation: Tuberculosis Research Centre, Respiratory Infections Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Lisa
authors.initials: L
authors.lastname: Grass
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Graham S
authors.initials: GS
authors.lastname: Cooke
authors.affiliation: Department of GU and HIV Medicine, The North West London Hospitals NHS Trust, London, United Kingdom.
authors.forename: Moses S
authors.initials: MS
authors.lastname: Kapembwa
authors.affiliation: Tuberculosis Service, St Mary's Hospital, Imperial College Healthcare Trust, London, United Kingdom.
authors.forename: Onn M
authors.initials: OM
authors.lastname: Kon
authors.affiliation: Centre for Respiratory Infection, Flow Cytometry Facility, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Sampson
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Graham P
authors.initials: GP
authors.lastname: Taylor
authors.affiliation: Tuberculosis Research Centre, Respiratory Infections Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Ajit
authors.initials: A
authors.lastname: Lalvani
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000382:microbiology*; D060085:Coinfection / Q000382:microbiology / Q000821:virology; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000097:blood* / Q000150:complications; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D055985:Latent Tuberculosis / Q000097:blood / Q000150:complications; D016131:Lymphocyte Subsets / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D014376:Tuberculosis / Q000097:blood* / Q000150:complications; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D007376:Interleukin-2; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma