Bronchoalveolar CD4+ T cell responses to respiratory antigens are impaired in HIV-infected adults. Issue 5 (25th February 2011)

• Record Type: Journal Article
• Authors: Jambo, Kondwani C; Sepako, Enoch; Fullerton, Duncan G; Mzinza, David; Glennie, Sarah; Wright, Adam K; Heyderman, Robert S; Gordon, Stephen B
• Is Part Of: Thorax. Volume 66:Issue 5(2011)
• Page Start: 375
• Page End: 382
• Publication Date: 2011-02-25
• Subjects: HIV -- human -- lung -- T cells -- bronchoalveolar lavage -- mucosa -- bronchoscopy -- immunodeficiency -- lymphocyte biology -- pneumonia -- respiratory infection; Chest -- Diseases -- Periodicals; Thorax; Chest -- Diseases; Periodicals; Periodicals; 617.54
• DOI: 10.1136/thx.2010.153825
• Languages: English
• ISSNs: 0040-6376

Abstract

Abstract : Rationale: 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. Main 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.