title: Bronchoalveolar CD4+ T cell responses to respiratory antigens are impaired in HIV-infected adults.
abstract: BACKGROUND
  HIV-infected adults are at an increased risk of lower respiratory tract infections. HIV infection impairs systemic acquired immunity, but there is limited information in humans on HIV-related cell-mediated immune defects in the lung.
  
  
  OBJECTIVE
  To investigate antigen-specific CD4(+) T cell responses to influenza virus, Streptococcus pneumoniae and Mycobacterium tuberculosis antigens in bronchoalveolar lavage (BAL) and peripheral blood between HIV-infected individuals and HIV-uninfected Malawian adults.
  
  
  METHODS
  We obtained BAL fluid and blood from HIV-infected individuals (n=21) and HIV-uninfected adults (n=24). We determined the proportion of T cell subsets including naive, memory and regulatory T cells using flow cytometry, and used intracellular cytokine staining to identify CD4(+) T cells recognising influenza virus-, S pneumoniae- and M tuberculosis-antigens.
  
  
  RESULTS
  CD4(+) T cells in BAL were predominantly of effector memory phenotype compared to blood, irrespective of HIV status (p<0.001). There was immune compartmentalisation with a higher frequency of antigen-specific CD4(+) T cells against influenza virus, S pneumoniae and M tuberculosis retained in BAL compared to blood in HIV-uninfected adults (p<0.001 in each case). Influenza virus- and M tuberculosis-specific CD4(+) T cell responses in BAL were impaired in HIV-infected individuals: proportions of total antigen-specific CD4(+) T cells and of polyfunctional IFN-γ and TNF-α-secreting cells were lower in HIV-infected individuals than in HIV-uninfected adults (p<0.05 in each case).
  
  
  CONCLUSIONS
  BAL antigen-specific CD4(+) T cell responses against important viral and bacterial respiratory pathogens are impaired in HIV-infected adults. This might contribute to the susceptibility of HIV-infected adults to lower respiratory tract infections such as pneumonia and tuberculosis.
authors.affiliation: Respiratory Infection Group, Liverpool School of Tropical Medicine, Pembroke Place, L3 5QA, Liverpool, UK. kjambo@liv.ac.uk
authors.forename: Kondwani C
authors.initials: KC
authors.lastname: Jambo
authors.forename: Enoch
authors.initials: E
authors.lastname: Sepako
authors.forename: Duncan G
authors.initials: DG
authors.lastname: Fullerton
authors.forename: David
authors.initials: D
authors.lastname: Mzinza
authors.forename: Sarah
authors.initials: S
authors.lastname: Glennie
authors.forename: Adam K
authors.initials: AK
authors.lastname: Wright
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gordon
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009975:Orthomyxoviridae / Q000276:immunology; D011023:Pneumonia, Staphylococcal / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D000956:Antigens, Viral; D016207:Cytokines