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

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

Correspondence and requests for reprints should be addressed to Robert J. Wilkinson, F.R.C.P., Room 3.03.05 Wolfson Pavilion, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa. 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 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- 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- or tumor necrosis factor (TNF)-, as well as polyfunctional cells, expressing IFN-, TNF-, 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

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject The risk of tuberculosis in HIV-infected persons is known to increase as the peripheral CD4 count declines. However, little is known of HIV-related immune defects in the lung, the initial site of mycobacterial infection. What This Study Adds to the Field This study compared lung innate and acquired immune responses in HIV-infected and HIV-uninfected persons living in an endemic area. We report a decreased frequency and function of mycobacteria-specific pulmonary CD4 T cells in HIV-1–infected persons.

 

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