HIV-1 Infection Impairs the Bronchoalveolar T-Cell Response to Mycobacteria

Abstract

The risk of developing active tuberculosis in persons with latent Mycobacterium tuberculosis infection is substantially increased shortly after HIV-1 seroconversion. Immune responses in the lung are important to restrict the growth of M. tuberculosis to prevent the development of disease. To investigate innate and adaptive immune responses to M. tuberculosis in bronchoalveolar lavage from HIV-1-infected persons without active tuberculosis. Peripheral blood was drawn and bronchoalveolar lavage (BAL) performed on healthy, HIV-1-uninfected (n = 21) and HIV-1-infected (n = 15) adults. Growth of M. tuberculosis was assessed in monocytes and alveolar macrophages. Cytokine expression by mycobacteria-specific CD4 and CD8 T cells was measured by intracellular cytokine staining or IFN-gamma ELISpot. Mycobacterial growth in monocytes or alveolar macrophages from HIV-1-infected and -uninfected persons did not differ. Total CD4 T-cell frequencies in BAL were lower in HIV-1-infected than in HIV-1-uninfected persons (P < 0.001). Mycobacteria (bacillus Calmette-Guérin)-specific CD4 T-cell responses in BAL were severely impaired: Frequencies of cells expressing IFN-gamma or tumor necrosis factor (TNF)-alpha, as well as polyfunctional cells, expressing IFN-gamma, TNF-alpha, and IL-2 together, were lower in HIV-1-infected persons than in uninfected controls (P < 0.01 for all). In addition to a total CD4 T-cell deficit, the function of mycobacteria-specific CD4 T cells is significantly impaired in the lung of HIV-1-infected persons, which may account for the HIV-1-associated elevated risk for developing tuberculosis.