ヒトT細胞白血病ウイルスI型のシェ-グレン症候群発症機序解明と治療法に関する研究

1994 Fiscal Year Annual Research Report

• Project/Area Number: 05670426
• Research Institution: The First Department of Internal Medicine, Nagasaki University School of Medicine
• Principal Investigator: 江口 勝美 長崎大学, 医学部, 助教授 (30128160)
• Co-Investigator(Kenkyū-buntansha): 寺田 馨 長崎大学, 医学部, 助手 (00236994) ; 河部 庸次郎 長崎大学, 医学部, 助手 (50244059)
• Keywords: ヒトT細胞白血病ウイルスI型 / シェ-グレン症候群 / Tax遺伝子 / 抗HTLV-I抗体 / 血管内皮細胞 / 接着分子 / サイトカイン / 合胞体形成

Research Abstract

A-I. HTLV-I感染におけるSjS発症機序の解明
疫 学: 長崎におけるSjS患者の中に占めるHTLV-I感染者の比率はコントロールに比べ有意に高く、特に50才以下の若年者群において高かった。
臨床症状: 抗HTLV-I抗体陽性SjSはブドウ膜炎、HTLV-I関連脊髄症(HAM)、繰り返す発熱などの腺外症状を伴いやすい。
抗HTLV-I抗体: 血清中の抗体価はHTLV-Iキャリアーより有意に高く、IgM抗体陽性もHAMと同等に高かった。唾液中の抗体価はIgA抗体が特異的に高かった。
HTLV-I provirus DNA: 末梢血単核球のprovirus DNA量はHTLV-Iキャリアーと同等でHAMほど高くなかった。唾液中のHTLV-IプロウイルスDNAの検出率はHAMと比較して低かった。
A-III. HTLV-I pX遺伝子導入
COS細胞やU937細胞にTax発現プラスミドとCAT遺伝子の上流にヒトIL-6遺伝子プロモーター/エンハンサー領域を挿入したレポータープラスミドをコントランスフェクションしておこなったCATアッセイによりIL-6遺伝子プロモーター/エンハンサー領域にTaxがトランスに作用することを明らかにした。
A-IV. 血管内皮細胞へのin vitroでのHTLV-I感染
血管内皮細胞をヒト帯静脈から分離し、HTLV-I感染T細胞株(MT-2細胞)と2日間混合培養した。この血管内皮細胞にHTLV-Iがトランスミッションし、同時にIL-1α、IL-6、G-CSF、GM-CSFを多量に産生した。
B. HTLV-I感染機序の解析とその感染防御についての検討
合胞体形成の系で、抗ICAM-3抗体が合胞体形成を抑制することを見い出した。

Research Products

• [Publications] Katsumi Eguchi,et al: "Stimulation of mitogenesis in human thyroid epithelial cells by endothelin" Acta Endocrinologica. 128(3). 215-220 (1993)
• [Publications] Takahiko Aoyagi,et al: "Immunolocalization of adhesion molecules in rheumatoid and osteoarthritic synovial tissues" Acta Medica Nagsakiensia. 38(2-4). 62-70 (1993)
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• [Publications] Yuji Nagayama,et al: "In vivo effect of gold compounds on thyroxine to triiodothyronine conversion by type I 5´-deiodinase in patients with rheumatoid arthritis" Hormone and Metabolic Research. 25. 654-650 (1993)
• [Publications] Masahiro Sakai,et al: "Infection of human synovial cells by human T cell lymphotropic virus type I: proliferation and granulocyte/macrophage colony-stimulating factor production by synovial cells" The Journal of Clinical Investigation. 92. 1957-1966 (1993)
• [Publications] Munetoshi Nakashima,et al: "Expression of basic fibroblast growth factor in synovial tissues from patients with rheumatoid arthritis:detection by immunohistological staining and in situ hybridisation" Annals of the Rheumatic Disease. 53(1). 45-50 (1994)
• [Publications] Takahiko Aoyagi,et al: "Treatment of patients with polyarthritis and anti-HTLV-I antibodies with interferon-alpha" Annals of the Rheumatic Disease. 53(1). 80-81 (1994)
• [Publications] Hironori Shimada,et al: "Interleukin 4 increases human synovial cell expression VCAM-1 and T cell binding" Annals of the Rheumatic Disease. 53. 601-607 (1994)
• [Publications] Yukitaka Ueki,et al: "Increment of CD8^+S6F1^+cells in synovial fluid from patients with rheumatoid arthritis" Annals of the Rheumatic Disease. 53. 816-822 (1994)
• [Publications] Hiroaki Ida,et al: "Mechanism of inhibitory effect of dextran sulfate and heparin on human T-cell lymphotropic virus I (HTLV-I)-induced syncytium formation in vitro:role of cell-to-cell contact" Antiviral Research. 23(1). 143-159 (1994)
• [Publications] Izumi Yamashita,et al: "Transactivation of the human interleukin-6 gene by the human T-lymphotropic virus type I" Blood. 84(5). 1573-1578 (1994)
• [Publications] Munetoshi Nakashima,et al: "Expression of adhesion molecule ICAM-1(CD54)in thyroid papillary adenocarcinoma" Journal of Endocrinological Investigation. (in press). (1994)
• [Publications] Kiyoshi Migita,et al: "Prevention of anti-CD3 monoclonal antibody induced thymic apoptosis by protein tyrosine Kinase inhibitors" Journal of Immunology. 153. 3457-3465 (1994)
• [Publications] Yukitaka Uekia,et al: "Increase in adhesion moleculcs on CD4^+ cells and CD4^+ cell subsets in synovial fluid from patients with rheumatoid arthritis" Journal of Rheumatology. 21(6). 1003-1010 (1994)
• [Publications] Masahiro Sakai,et al: "Clinical characteristics and prognosis of secondary amyloidosis in patients with rheumatoid arthritis :renal involvement and therapy" Japanese Journal of Rheumatology. 5(3). 297-304 (1994)
• [Publications] Shigeru Katamine,et al: "HTLV-I proviral DNA in umbilical cord blood of babies born to carrier mothers" The Lancet. 343(8909). 1326-1327 (1994)
• [Publications] Kaoru Terada,et al: "Prevalence of serum and salivary antibodies to HTLV-I in Sjogren´s syndrome" The Lancet. 344. 1116-1119 (1994)
• [Publications] Munetoshi Nakashima,et al: "The expression of adhesion molecules in thyroid glands from patients with Graves´disease" Thyroid. 4(1). 19-25 (1994)
• [Publications] Tomoki Origuchi,et al: "Synovial cells are potent antigen-prsenting cells for superantigens, staphylococal enterotoxin B" Clinical and Experimental Immunology. (accepted). (1994)
• [Publications] Souko Sakito,et al: "Serum cytokines in patients with rheumatoid arthritis: correlation of interferon γ and tumor necrosis factor α with the characteristics of peripheral blood mononuclear cells" Rheumatology International. 15(in press). (1995)
• [Publications] Katsumi Eguchi,et al: "Autoimmune Endocrine Disease" P Kendall-Taylor, 34 (1995)
• [Publications] Katsumi Eguchi,et al: "80 years of Hashimoto Disease" S.Nagataki,T.Mori,K.Torizuk, 4 (1993)
• [Publications] Hiroaki Ida,et al: "Proceeding of 5th International Conference on Human Differentiation Antigens" (in press), (1994)