Multiple mycobacterial antigens are targets of the adaptive immune response in pulmonary sarcoidosis |
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Authors: | Kyra A Oswald-Richter Dia C Beachboard Xiaoyan Zhan Christa F Gaskill Susamma Abraham Cathy Jenkins Daniel A Culver Wonder Drake |
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Institution: | 1.Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232-2363, USA;2.Division of Infectious Diseases and Department of Medicine, Vanderbilt University Medical School, Nashville, TN 37232-2363, USA;3.Respiratory Institute, Cleveland Clinic, Cleveland, OH 44195, USA;4.Department of Biostatistics, Vanderbilt University Medical School, Nashville, TN 37232-2363, USA |
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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. |
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