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Am J Respir Crit Care Med. 2009 Dec 15;180(12):1262-70. doi: 10.1164/rccm.200907-1011OC. Epub 2009 Sep 24.

HIV-1 infection impairs the bronchoalveolar T-cell response to mycobacteria.

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  • 1Clinical Infectious Diseases Research Initiative, University of Cape Town, Observatory, South Africa.

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-gamma 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-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).

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.

PMID:
19797156
[PubMed - indexed for MEDLINE]
PMCID:
PMC2796736
Free PMC Article
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