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

Antigen-specific multifunctional T-cells in sarcoidosis patients with Löfgren’s syndrome

“…For example, it was shown that BAL cells from sarcoidosis patients reacted to mycobacterial antigens but not to keyhole limpet haemocyanin, demonstrating antigen specificity [13,28]. Likewise, peripheral blood cells from a majority of sarcoidosis patients responded to stimulation with mycobacterial antigens but not lysate from Trypanosoma brucei [29].…”

“…Recently, SONG et al [11] identified a specific protein, mycobacterial catalase-peroxidase (mKatG), in sarcoidosis tissue but not in healthy subjects. T-cell responses against mKatG have been observed in sarcoidosis lung [12,13] and peripheral blood mononuclear cells [14], but the specificity of Tcells responding to mKatG has not been characterised in detail. Although we have data to support that AV2S3+ T-cells can recognise mycobacterial antigens [15], we have not been able to firmly establish the specificity of the AV2S3+ lung T-cells.…”

Programmed Death-1 Inhibition of Phosphatidylinositol 3-Kinase/AKT/Mechanistic Target of Rapamycin Signaling Impairs Sarcoidosis CD4+ T Cell Proliferation

“…Numerous elegant studies demonstrate that sarcoidosis T cells have increased cytokine production, as well as evidence of TCR stimulation (22,23). These studies have been complemented by molecular analyses demonstrating that microbial antigens are present within sarcoidosis granulomas (24)(25)(26)(27)(28) and that these same antigens are targets of the sarcoidosis adaptive immune response (14,26,(29)(30)(31). The expression of Th1 cytokines is the healthy adaptive immune response attempt to signal immune mediators that can clear foreign antigen, leading to its clearance.…”

Evidence for Mycobacteria in Sarcoidosis

“…Drake and colleagues reported that peripheral blood mononuclear cells (PBMNs) from 15 of 26 patients with sarcoidosis responded to peptides from the mycobacterial antigens ESAT-6 and/or mKatG, compared with 1 of 24 purified protein derivative (PPD)-negative control subjects (92). The same group observed higher rates of ESAT-6 and mKatG-dependent T-cell activation and proliferation in BAL samples from patients with sarcoidosis versus control subjects (93). It was further shown that CD41 T cells mediated a Th 1 response in patients with sarcoidosis when these peptide antigens were presented by DRB1*1101-expressing antigen-presenting cells (94).…”

“…These findings suggest the possibility that immune cells isolated from diseased lungs possess a general hyperreactivity that is not specific to mycobacterial antigens. However, Drake and colleagues detected mycobacterial antigen-evoked cellular immune responses in cells from patients with sarcoidosis who did not react to Trypanosoma brucei lysates (96) or the neoantigen keyhole limpet hemocyanin (93), demonstrating antigen specificity in the immune response.…”