Expression of costimulatory molecules (4-1BBL and Fas) and major histocompatibility class I chain-related A (MICA) in aortic tissue with Takayasu's arteritis.
To further investigate the immunological mechanisms involved, we analyzed the expression of costimulatory molecules in aortic tissue and their counterpart molecules on infiltrating cells of patients with Takayasu's arteritis. We also examined the expression of major histocompatibility complex (MHC) class I chain-related (MIC) A in aortic tissue, which is known to be induced by external stress, and its counterpart NKG2D receptors on infiltrating cells. Among these costimulatory molecules, strong expression of 4-1BBL and Fas was induced in the aortic tissue, and most of the infiltrating cells expressed 4-1BB and FasL, suggesting these pathways play critical roles in T-cell-mediated vascular injury. We also found that MICA was strongly induced in the aortic tissue and that at least part of the infiltrating cells expressed NKG2D receptors. Some infiltrating cells - but not vascular smooth muscle cells - seemed to have undergone apoptosis. Our findings strongly suggest that 4-1BB/4-1BBL and Fas/FasL pathways play important roles in vascular injury in Takayasu's arteritis. We assume that gammadelta T cells infiltrated aortic tissue recognizing MICA, resulting in the induction of MHC antigens and costimulatory molecules, and then alphabeta T-cells infiltrated recognizing some auto-antigens presented by MHC antigens, leading to chronic inflammation.
Seko
Yoshinori
Y
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. sekoyosh-tky@umin.ac.jp
Sugishita
Kazuyuki
K
Sato
Osamu
O
Takagi
Atsuhiko
A
Tada
Yusuke
Y
Matsuo
Hiroshi
H
Yagita
Hideo
H
Okumura
Ko
K
Nagai
Ryozo
R
D053330:4-1BB Ligand; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D001011:Aorta / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000276:immunology; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D053282:CD27 Ligand; D053285:CD30 Ligand; D019013:CD40 Antigens / Q000378:metabolism; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K; D053278:OX40 Ligand; D011971:Receptors, Immunologic / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D013625:Takayasu Arteritis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
D053330:4-1BB Ligand; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D053282:CD27 Ligand; D053285:CD30 Ligand; D019013:CD40 Antigens; C505771:CD70 protein, human; C497964:CD86 protein, human; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D053278:OX40 Ligand; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C089251:TNFSF4 protein, human; C505774:TNFSF8 protein, human; C505974:TNFSF9 protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor