Expression of OX40 in muscles of polymyositis and granulomatous myopathy.
OX40 is selectively expressed on activated autoreactive memory T cells and these OX40+ lymphocytes may play a crucial role in autoimmune diseases. To determine whether OX40+ lymphocytes are involved in the pathomechanism of human inflammatory muscle diseases, we immunohistochemically examined the distribution of OX40+ cells in muscles from patients with polymyositis and granulomatous myopathy, and compared with that of cells bearing other activation markers, such as IL-2 receptor (IL-2R) and HLA-DR. In polymyositis, OX40+ mononuclear cells were found predominantly in the perivascular sites and to a lesser degree in the endomysium. Scanty IL-2R+ mononuclear cells were located only in the endomysium and HLA-DR was expressed on half of the mononuclear cells distributed diffusely in the perivascular sites and in the endomysium. Mononuclear cell infiltration in the perivascular sites was greater in the muscles in which OX40+ cells were present in the perivascular sites than in those without OX40+ cells in the perivascular sites (p<0.05). In granulomatous myopathy, OX40+ cells were detected in the centers of the granulomas. In contrast, IL-2R+ cells were present at the periphery of the granulomas and HLA-DR was detected on mononuclear cells throughout the granulomas. OX40+ mononuclear cells with specific distributions in muscles may be involved in the pathomechanism of polymyositis and granulomatous myopathy, and can be a candidate molecule of selective immunotherapy in these diseases.
Tateyama
Maki
M
Department of Neurology, Tohoku University School of Medicine, 1-1, Seiryo-machi, Aoba-ku, 980-8574, Sendai, Japan. mtateyama@neurol.med.tohoku.ac.jp
Fujihara
Kazuo
K
Ishii
Naoto
N
Sugamura
Kazuo
K
Onodera
Yoshiaki
Y
Itoyama
Yasuto
Y
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D005260:Female; D006099:Granuloma / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009135:Muscular Diseases / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D017285:Polymyositis / Q000378:metabolism* / Q000473:pathology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis / Q000096:biosynthesis*
D015415:Biomarkers; D006684:HLA-DR Antigens; D015375:Receptors, Interleukin-2; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7