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Infection and Immunity, September 2009, p. 3740-3748, Vol. 77, No. 9
0019-9567/09/$08.00+0 doi:10.1128/IAI.00142-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Cellular Responses to Mycobacterial Antigens Are Present in Bronchoalveolar Lavage Fluid Used in the Diagnosis of Sarcoidosis
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Kyra A. Oswald-Richter,1*
Daniel A. Culver,2
Charlene Hawkins,1
Rana Hajizadeh,1
Susamma Abraham,2
Bryan E. Shepherd,3
Cathy A. Jenkins,3
Marc A. Judson,4 and
Wonder P. Drake1,5
Division of Infectious Diseases and Department of Medicine, Vanderbilt University Medical School, Nashville, Tennessee 37232-2363,1 Respiratory Institute, Cleveland Clinic, Cleveland, Ohio 44195,2 Department of Biostatistics, Vanderbilt University Medical School, Nashville, Tennessee 37232-2363,3 Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, South Carolina 29425,4 Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-23635
Received 5 February 2009/ Returned for modification 27 March 2009/ Accepted 9 June 2009
Considerable evidence supports the concept that CD4+ T cells are important in sarcoidosis pathogenesis, but the antigens responsible for the observed Th1 immunophenotype remain elusive. The epidemiologic association with bioaerosols and the presence of granulomatous inflammation support consideration of mycobacterial antigens. To explore the role of mycobacterial antigens in sarcoidosis immunopathogenesis, we assessed the immune recognition of mycobacterial antigens, the 6-kDa early secreted antigenic protein (ESAT-6) and catalase-peroxidase (KatG), by T cells derived from bronchoalveolar lavage (BAL) fluid obtained during diagnostic bronchoscopy. We report the presence of antigen-specific recognition of ESAT-6 and KatG in T cells from BAL fluid of 32/44 sarcoidosis subjects, compared to 1/27 controls (P < 0.0001). CD4+ T cells were primarily responsible for immune recognition (32/44 sarcoidosis subjects), although CD8+ T-cell responses were observed (25/41 sarcoidosis subjects). Recognition was significantly absent from BAL fluid cells of patients with other lung diseases, including infectious granulomatous diseases. Blocking of Toll-like receptor 2 reduced the strength of the observed immune response. The presence of immune responses to mycobacterial antigens in cells from BAL fluid used for sarcoidosis diagnosis suggests a strong association between mycobacteria and sarcoidosis pathogenesis. Inhibition of immune recognition with monoclonal antibody against Toll-like receptor 2 suggests that induction of innate immunity by mycobacteria contributes to the polarized Th1 immune response.
* Corresponding author. Mailing address: Division of Infectious Diseases, Vanderbilt University Medical School, 21st Avenue South, Medical Center North, Room A-3314, Nashville, TN 37232-2363. Phone: (615) 322-5266. Fax: (615) 343-6160. E-mail: Kyra.Richter{at}vanderbilt.edu
Published ahead of print on 13 July 2009.
Supplemental material for this article may be found at http://iai.asm.org/.
Infection and Immunity, September 2009, p. 3740-3748, Vol. 77, No. 9
0019-9567/09/$08.00+0 doi:10.1128/IAI.00142-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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