1995 Fiscal Year Annual Research Report

慢性関節リウマチの病因遺伝子の構造と機能の解析

Research Project

Project/Area Number	06044208
Research Institution	St. Marianna University School of Medicine
Principal Investigator	西岡久寿樹聖マリアンナ医科大学, 難病治療研究センター・臨床遺伝部門, 教授 (60049070)
Co-Investigator(Kenkyū-buntansha)	森本幾夫ハーバード大学, 癌研究所, 準教授 KRIEG Arthur アイオワ大学, 医学部, 教授 GAY Steffen アラバマ大学, 医学部・リウマチ科, 教授
Keywords	HTLV-I tax遺伝子 / 滑膜増殖 / アポトーシス / Fas抗原 / 骨関節破壊
Research Abstract	我々のグループは、ヒト成人T細胞白血病ウイルス(HTLV-I)感染者に認められる免疫異常を伴った関節症をHTLV-I associated arthropathy(HAAP)という疾患概念を提唱し、次いでその病態・病理像を発表した。その後、慢性関節リウマチ(RA)にみられる滑膜細胞の増殖機序とHTLV-Iの関連を検討し、本年度は正常滑膜細胞に遺伝子導入を行なうことにより、以下の点を明らかにした。 1.HTLV-Iプロウイルスの調節遺伝子であるtax遺伝子に滑膜細胞の増殖機序の存在 2.滑膜細胞の抗原提示能の誘導 3.アポトーシスの調節機能障害機構 4.c-fos遺伝子の活性化による滑膜増殖誘導能 5.HTLV-I関節症に関する分子疫学の視点からKrieg博士と、分子免疫の視点からUABのGay教授と協同研究を行ない、RA滑膜組織におけるT細胞のactivation機構についての解析を行なった。 6.HTLV-I感染とリウマチとの疫学的因果関係をKreig教授との協同研究により明らかにした。

Research Products
(12 results)

All Other

All Publications (12 results)

[Publications] Murata H,et al.: "Limited T Cell Receptor Repertoire of Infiltrating T Cells in the Kidneys of Sjogren's Syndrome Patents with Interstitial Nephritis." J.Immunol.155. 4084-4089 (1995)
[Publications] Yamamoto K,et al.: "Accumulation of Distinct T cell Clonotypes in Human Solid Tumors." J.Immunol.154. 1804-1809 (1995)
[Publications] Nakajima T,et al.: "Apoptosis and Functional Fas Antigen in Rheumatoid Arthritis Synoviocytes." Arthritis Rheum. 38. 485-491 (1995)
[Publications] Yamamoto K,et al.: "Oligoclonal Proliferation of Human T cell Leukemia Virus Type I Infected Lymphocytes in Lesions of Virus-Induced Arthropathy." Biochemical and Biophysical Research Communications. 208. 1040-1045 (1995)
[Publications] Koto T,et al.: "Autoepitopes of the 52-kd SS-A/Ro Molecule." Arthritis Rheum. 38. 990-998 (1995)
[Publications] Sumida T,et al.: "Selective Reduction of T Cells Bearing Invariant V α 24J α Q Antigen Receptor in Patients with Systemic Sclerosis." J.Exp.Med.182. 1163-1168 (1995)
[Publications] Namekawa T,et al.: "Identification of Ro(SSA)52kDa Reactive T Cells in Labial Salivary Glands from Patients with SjogrenSyndrome." J Rheumatol. 22. 2092-2099 (1995)
[Publications] Masuko K,et al.: "Stable Clonal Expansion of T Cells induced by Bone Marrow Transplantation." Blood. 87. 789-799 (1996)
[Publications] Aono H,et al.: "Direct suppression of Human Synovial Cell Proliferation in Vitro by Salazosulfapyridine and Bacillamine." J Rheumatol. 22. 65-70 (1996)
[Publications] Ikeda Y,et al.: "High Frequencies of Identical T Cell Clonotypes in Synovial Tissues of Rheumatoid Arthritis Patients Suggest the Occurrence of Common Antigen-driven Immune Responses." Arthritis Rheum. (in press).
[Publications] Fujisawa K,et al.: "Activation of Transcription Factor NF-kB in Human Synovial Cells in Response to Tumor Necrosis Factor-alpha." Arthritis Rheum. (in press).
[Publications] Nishioka K,et al.: "Human T Cell Leukemia Virus Type-I in Arthropathy and Autoimmune Disorders." Arthritis Rheum. (in press).

1995 Fiscal Year Annual Research Report

慢性関節リウマチの病因遺伝子の構造と機能の解析

Principal Investigator

西岡 久寿樹 聖マリアンナ医科大学, 難病治療研究センター・臨床遺伝部門, 教授 (60049070)

Research Products

[Publications] Murata H,et al.: "Limited T Cell Receptor Repertoire of Infiltrating T Cells in the Kidneys of Sjogren's Syndrome Patents with Interstitial Nephritis." J.Immunol.155. 4084-4089 (1995)

[Publications] Yamamoto K,et al.: "Accumulation of Distinct T cell Clonotypes in Human Solid Tumors." J.Immunol.154. 1804-1809 (1995)

[Publications] Nakajima T,et al.: "Apoptosis and Functional Fas Antigen in Rheumatoid Arthritis Synoviocytes." Arthritis Rheum. 38. 485-491 (1995)

[Publications] Yamamoto K,et al.: "Oligoclonal Proliferation of Human T cell Leukemia Virus Type I Infected Lymphocytes in Lesions of Virus-Induced Arthropathy." Biochemical and Biophysical Research Communications. 208. 1040-1045 (1995)

[Publications] Koto T,et al.: "Autoepitopes of the 52-kd SS-A/Ro Molecule." Arthritis Rheum. 38. 990-998 (1995)

[Publications] Sumida T,et al.: "Selective Reduction of T Cells Bearing Invariant V α 24J α Q Antigen Receptor in Patients with Systemic Sclerosis." J.Exp.Med.182. 1163-1168 (1995)

[Publications] Namekawa T,et al.: "Identification of Ro(SSA)52kDa Reactive T Cells in Labial Salivary Glands from Patients with SjogrenSyndrome." J Rheumatol. 22. 2092-2099 (1995)

[Publications] Masuko K,et al.: "Stable Clonal Expansion of T Cells induced by Bone Marrow Transplantation." Blood. 87. 789-799 (1996)

[Publications] Aono H,et al.: "Direct suppression of Human Synovial Cell Proliferation in Vitro by Salazosulfapyridine and Bacillamine." J Rheumatol. 22. 65-70 (1996)

[Publications] Ikeda Y,et al.: "High Frequencies of Identical T Cell Clonotypes in Synovial Tissues of Rheumatoid Arthritis Patients Suggest the Occurrence of Common Antigen-driven Immune Responses." Arthritis Rheum. (in press).

[Publications] Fujisawa K,et al.: "Activation of Transcription Factor NF-kB in Human Synovial Cells in Response to Tumor Necrosis Factor-alpha." Arthritis Rheum. (in press).

[Publications] Nishioka K,et al.: "Human T Cell Leukemia Virus Type-I in Arthropathy and Autoimmune Disorders." Arthritis Rheum. (in press).

西岡久寿樹聖マリアンナ医科大学, 難病治療研究センター・臨床遺伝部門, 教授 (60049070)