title: Peripheral blood responses to specific antigens and CD28 in sarcoidosis.
abstract: BACKGROUND
  Potential antigens inducing sarcoid inflammation include mycobacterial and auto-antigens. Paradoxically, peripheral anergy to common recall antigens also occurs, possibly due to impaired dendritic cell or regulatory T-cell responses, or impaired T-cell co-stimulation. The purpose of this study was to compare peripheral blood responses of patients with sarcoidosis to candidate antigens, and examine CD28 T-cell co-stimulation.
  
  
  METHODS
  Peripheral blood mononuclear cell (PBMC) responses were examined from patients with sarcoidosis (n=16) and healthy control subjects (n=22) following PBMC stimulation with: anti-CD3/CD28 coated beads; Mycobacterium tuberculosis ESAT-6 and KatG peptides; vimentin and lysyl tRNA peptides; and common recall antigens, including cytomegalovirus (CMV) cell lysate as well as CMV, Epstein-Barr virus, influenza virus (CEF) peptides.
  
  
  RESULTS
  ESAT-6/KatG peptide stimulation induced greater numbers of IFN-γ producing T-cells, and elevated IL-2, IL-6 and TNF-α production in sarcoidosis compared to purified protein derivative (PPD)-negative healthy control subjects. PBMCs from patients with sarcoidosis showed reduced IFN-γ producing T-cells following stimulation with CMV lysate, CEF peptides and CD3/CD28 beads; and reduced IL-4 and TNF-α production following CD3/CD28 activation.
  
  
  CONCLUSIONS
  Patients with sarcoidosis exhibit greater PBMC responses to M. tuberculosis antigens compared to PPD-negative controls, but reduced T-cell responses to common recall antigens. One contributing mechanism may be impairment of T-cell CD28 co-stimulation.
authors.affiliation: Inflammation and Infection Research Centre (IIRC), Faculty of Medicine, University of New South Wales, Sydney, NSW, 2052, Australia. h.ahmadzai@unsw.edu.au
authors.forename: Hasib
authors.initials: H
authors.lastname: Ahmadzai
authors.forename: Barbara
authors.initials: B
authors.lastname: Cameron
authors.forename: Jeanie J Y
authors.initials: JJ
authors.lastname: Chui
authors.forename: Andrew
authors.initials: A
authors.lastname: Lloyd
authors.forename: Denis
authors.initials: D
authors.lastname: Wakefield
authors.forename: Paul S
authors.initials: PS
authors.lastname: Thomas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D012507:Sarcoidosis / Q000276:immunology* / Q000503:physiopathology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014797:Vital Capacity / Q000502:physiology; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D001324:Autoantigens; D018106:CD28 Antigens; D016207:Cytokines; D007371:Interferon-gamma