title: Differences in antigen-specific CD4+ responses to opportunistic infections in HIV infection.
abstract: HIV-infected individuals with severe immunodeficiency are at risk of opportunistic infection (OI). Tuberculosis (TB) may occur without substantial immune suppression suggesting an early and sustained adverse impact of HIV on Mycobacterium tuberculosis (MTB)-specific cell mediated immunity (CMI). This prospective observational cohort study aimed to observe differences in OI-specific and MTB-specific CMI that might underlie this. Using polychromatic flow cytometry, we compared CD4+ responses to MTB, cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Candida albicans in individuals with and without HIV infection. MTB-specific CD4+ T-cells were more polyfunctional than virus specific (CMV/EBV) CD4+ T-cells which predominantly secreted IFN-gamma (IFN-γ) only. There was a reduced frequency of IFN-γ and IL-2 (IL-2)-dual-MTB-specific cells in HIV-infected individuals, which was not apparent for the other pathogens. MTB-specific cells were less differentiated especially compared with CMV-specific cells. CD127 expression was relatively less frequent on MTB-specific cells in HIV co-infection. MTB-specific CD4+ T-cells PD-1 expression was infrequent in contrast to EBV-specific CD4+ T-cells. The variation in the inherent quality of these CD4+ T-cell responses and impact of HIV co-infection may contribute to the timing of co-infectious diseases in HIV infection.
authors.affiliation: Tuberculosis Research Centre Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London London, UK.
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Pollock
authors.affiliation: Tuberculosis Research Centre Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London London, UK.
authors.forename: Damien J
authors.initials: DJ
authors.lastname: Montamat-Sicotte
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Imperial College London London, UK.
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, UK.
authors.forename: Moses S
authors.initials: MS
authors.lastname: Kapembwa
authors.affiliation: Tuberculosis Service, St Mary's Hospital, Imperial College Healthcare NHS Trust London, UK.
authors.forename: Onn M
authors.initials: OM
authors.lastname: Kon
authors.affiliation: Tuberculosis Research Centre Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London London, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Grass
authors.affiliation: Centre for Respiratory Infection, Flow Cytometry Facility, National Heart and Lung Institute, Imperial College London London, UK.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Sampson
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Imperial College London London, UK.
authors.forename: Graham P
authors.initials: GP
authors.lastname: Taylor
authors.affiliation: Tuberculosis Research Centre Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London London, UK.
authors.forename: Ajit
authors.initials: A
authors.lastname: Lalvani
keywords: Candida albicans; Epstein-Barr virus; HIV; Mycobacterium tuberculosis; cytomegalovirus