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Published ahead of print on September 24, 2009
Am. J. Respir. Crit. Care Med. 2009, doi:10.1164/rccm.200907-1011OC
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Submitted on July 5, 2009
Accepted on September 23, 2009

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

Barbara Kalsdorf1, Thomas J Scriba2, Kathryn Wood3, Cheryl L Day2, Keertan Dheda4, Rodney Dawson5, Willem A Hanekom2, Christophe Lange6, and Robert J Wilkinson7*

1 Clinical Infectious Diseases Research Initiative, University of Cape Town, Cape Town, South Africa; Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany, 2 South African Tuberculosis Vaccine Initiative and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa, 3 Clinical Infectious Diseases Research Initiative, University of Cape Town, Cape Town, South Africa, 4 CTBRI, University of Cape Town Lung Institute and Department of Medicine, University of Cape Town, Cape Town, South Africa; Centre for Infectious Diseases and International Health, UCL, London, United Kingdom, 5 CTBRI, University of Cape Town Lung Institute and Department of Medicine, University of Cape Town, Cape Town, South Africa, 6 Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany, 7 Clinical Infectious Diseases Research Initiative, University of Cape Town, Cape Town, South Africa; Division of Medicine, Imperial College London, London, United Kingdom; National Institute for Medical Research, Mill Hill, London, United Kingdom

* To whom correspondence should be addressed. E-mail: r.j.wilkinson{at}imperial.ac.uk.

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 Mycobacterium tuberculosis to prevent the development of disease. Objectives: To investigate innate and adaptive immune responses to Mycobacterium tuberculosis in bronchoalveolar lavage from HIV-1 infected persons without active tuberculosis. Methods: Peripheral blood was drawn and bronchoalveolar lavage performed on healthy, HIV-1 uninfected (n=21) and HIV-1 infected (n=15) adults. Growth of Mycobacterium 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 bronchoalveolar lavage were lower in HIV-1 infected than in HIV-1-uninfected persons (p<0.001). Mycobacteria (BCG)-specific CD4 T cell responses in bronchoalveolar lavage were severely impaired: Frequencies of cells expressing IFN-{gamma} or, 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.


Key words: HIV-1 • tuberculosis • Immunity mucosal • T-cells • macrophages







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