title: Activated myeloid dendritic cells accumulate and co-localize with CD3+ T cells in coronary artery lesions in patients with Kawasaki disease.
abstract: Emerging evidence implicating the participation of dendritic cells (DCs) and T cells in various vascular inflammatory diseases such as giant cell arteritis, Takayasu's arteritis, and atherosclerosis led us to hypothesize that they might also participate in the pathogenesis of coronary arteritis in Kawasaki disease (KD). Coronary artery specimens from 4 patients with KD and 6 control patients were obtained. Immunohistochemical and computer-assisted histomorphometric analyses were performed to detect all myeloid DCs (S-100(+), fascin(+)), all plasmacytoid DCs (CD123(+)) as well as specific DC subsets (mature myeloid DCs [CD83(+)], myeloid [BDCA-1(+)] and plasmacytoid DC precursors [BDCA-2(+)]), T cells (CD3(+)), and all antigen-presenting cells (HLA-DR(+)). Co-localization of DCs with T cells was assessed using double immunostaining. Significantly more myeloid DCs at a precursor, immature or mature stage were found in coronary lesions of KD patients than in controls. Myeloid DC precursors were distributed equally in the intima and adventitia. Mature myeloid DCs were particularly abundant in the adventitia. There was a significant correlation between mature DCs and HLA-DR expression. Double immunostaining demonstrated frequent contacts between myeloid DCs and T cells in the outer media and adventitia. Plasmacytoid DC precursors were rarely found in the adventitia. In conclusion, coronary artery lesions of KD patients contain increased numbers of mature myeloid DCs with high HLA-DR expression and frequent T cell contacts detected immunohistochemically. This suggests that mature arterial myeloid DCs might be activating T cells in situ and may be a significant factor in the pathogenesis of coronary arteritis in KD.
authors.affiliation: Medical Clinic II, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Atilla
authors.initials: A
authors.lastname: Yilmaz
authors.forename: Anne
authors.initials: A
authors.lastname: Rowley
authors.forename: Danica J
authors.initials: DJ
authors.lastname: Schulte
authors.forename: Terence M
authors.initials: TM
authors.lastname: Doherty
authors.forename: Nicolas W J
authors.initials: NW
authors.lastname: Schröder
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.forename: Mitra
authors.initials: M
authors.lastname: Kalelkar
authors.forename: Iwona
authors.initials: I
authors.lastname: Cicha
authors.forename: Katja
authors.initials: K
authors.lastname: Schubert
authors.forename: Werner G
authors.initials: WG
authors.lastname: Daniel
authors.forename: Christoph D
authors.initials: CD
authors.lastname: Garlichs
authors.forename: Moshe
authors.initials: M
authors.lastname: Arditi
mesh_terms: D000783:Aneurysm / Q000473:pathology; D017252:CD3 Complex / Q000378:metabolism*; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000378:metabolism* / Q000473:pathology; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
chemical_list: D017252:CD3 Complex; D006684:HLA-DR Antigens