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  • Title: Bronchoalveolar CD4+ T cell responses to respiratory antigens are impaired in HIV-infected adults.
    Author: Jambo KC, Sepako E, Fullerton DG, Mzinza D, Glennie S, Wright AK, Heyderman RS, Gordon SB.
    Journal: Thorax; 2011 May; 66(5):375-82. PubMed ID: 21357587.
    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.
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