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

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Abstract

Rationale:

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.

Objectives:

To investigate innate and adaptive immune responses to M. tuberculosis in bronchoalveolar lavage from HIV-1–infected persons without active tuberculosis.

Methods:

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-γ ELISpot.

Measurements and Main Results:

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-γ or tumor necrosis factor (TNF)-α, as well as polyfunctional cells, expressing IFN-γ, TNF-α, and IL-2 together, were lower in HIV-1–infected persons than in uninfected controls (P < 0.01 for all).

Conclusions:

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.

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