title: Multiple mycobacterial antigens are targets of the adaptive immune response in pulmonary sarcoidosis.
abstract: BACKGROUND
  Sarcoidosis 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.
  
  
  METHODS
  Fifty-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.
  
  
  RESULTS
  Alveolar 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.
  
  
  CONCLUSIONS
  Together 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.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232-2363, USA. kyra.richter@vanderbilt.edu
authors.forename: Kyra A
authors.initials: KA
authors.lastname: Oswald-Richter
authors.forename: Dia C
authors.initials: DC
authors.lastname: Beachboard
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhan
authors.forename: Christa F
authors.initials: CF
authors.lastname: Gaskill
authors.forename: Susamma
authors.initials: S
authors.lastname: Abraham
authors.forename: Cathy
authors.initials: C
authors.lastname: Jenkins
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Culver
authors.forename: Wonder
authors.initials: W
authors.lastname: Drake
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium / Q000276:immunology*; D017565:Sarcoidosis, Pulmonary / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial