Multiple mycobacterial antigens are targets of the adaptive immune response in pulmonary sarcoidosisReport as inadecuate




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Respiratory Research

, 11:161

First Online: 23 November 2010Received: 15 June 2010Accepted: 23 November 2010

Abstract

IntroductionSarcoidosis is a multisystem granulomatous disease for which the association with mycobacteria continues to strengthen. It is hypothesized that a single, poorly degradable antigen is responsible for sarcoidosis pathogenesis. Several reports from independent groups support mycobacterial antigens having a role in sarcoidosis pathogenesis. To identify other microbial targets of the adaptive immune response, we tested the ability of CD4+ and CD8+ T cells to recognize multiple mycobacterial antigens.

MethodsFifty-four subjects were enrolled in this study: 31 sarcoidosis patients, nine non-tuberculosis mycobacterial NTM infection controls, and 14 PPD- controls. Using flow cytometry, we assessed for Th1 immune responses to ESAT-6, katG, Ag85A, sodA, and HSP.

ResultsAlveolar T-cells from twenty-two of the 31 sarcoidosis patients produced a CD4+ response to at least one of ESAT-6, katG, Ag85A, sodA, or HSP, compared to two of 14 PPD- controls p = 0.0008 and five of nine NTM controls p = 0.44, while eighteen of the 31 sarcoidosis subjects tested produced a CD8+ response to at least one of the mycobacterial antigens compared to two of 14 PPD- controls p = 0.009 and three of nine NTM controls 0.26. Not only did the BAL-derived T cells respond to multiple virulence factors, but also to multiple, distinct epitopes within a given protein. The detection of proliferation upon stimulation with the mycobacterial virulence factors demonstrates that these responses are initiated by antigen specific recognition.

ConclusionsTogether these results reveal that antigen-specific CD4+ and CD8+ T cells responses to multiple mycobacterial epitopes are present within sites of active sarcoidosis involvement, and that these antigen-specific responses are present at the time of diagnosis.

Abbreviations used in this paperBALbronchoalveolar lavage

NTMnon-tuberculosis mycobacteria

PPDPurified Protein Derivative negative

ESAT-6early secreted antigenic target protein 6

katGcatalase-peroxidase

Ag85Amycolyl transferase Antigen 85A

sodAsuperoxide dismutase A

HPSheat shock protein

IFN-γinterferon-γ

SEBstaphylococcal enterotoxin B

KLHKeyhole Limpet Hemocyanin

CFSEcarboxyfluorescein succinimidyl ester

Electronic supplementary materialThe online version of this article doi:10.1186-1465-9921-11-161 contains supplementary material, which is available to authorized users.

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Author: Kyra A Oswald-Richter - Dia C Beachboard - Xiaoyan Zhan - Christa F Gaskill - Susamma Abraham - Cathy Jenkins - Daniel A

Source: https://link.springer.com/







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