Cellular responses to mycobacterial antigens are present in bronchoalveolar lavage fluid used in the diagnosis of sarcoidosis.

Abstract:

: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.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Oswald-Richter KA,Culver DA,Hawkins C,Hajizadeh R,Abraham S,Shepherd BE,Jenkins CA,Judson MA,Drake WP

doi

10.1128/IAI.00142-09

subject

Has Abstract

pub_date

2009-09-01 00:00:00

pages

3740-8

issue

9

eissn

0019-9567

issn

1098-5522

pii

IAI.00142-09

journal_volume

77

pub_type

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