1999 Fiscal Year Annual Research Report

Th1/Th2バランスからみたHAM発症分子機構の解明と治療法開発の基礎的検討

Research Project

Project/Area Number	10670593
Research Institution	Nagasaki University
Principal Investigator	中村龍文長崎大学, 医学部・附属病院, 講師 (00198219)
Co-Investigator(Kenkyū-buntansha)	江口勝美長崎大学, 医学部, 教授 (30128160) 調漸長崎大学, 医学部・附属病院, 助手 (40264220)
Keywords	HAM / CD4^+T-lymphocytes / matrix metalloproteinase-2 / Th1 / Th2balance / Fas / Fas ligand / pentoxifylline / VCAM-1 / VLA-4 / E-selectin ligand
Research Abstract	1;HAM患者末梢血CD4陽性Tリンパ球におけるE-selectin陽性細胞機能とHTLV-1感染との関係について HAM患者末梢血CD4陽性Tリンパ球では,Th1マーカーであるE-selectin ligand発現細胞が増加していることとそのE-selectin ligand陽性細胞の機能検索においてTh1サイトカインであるIFN-γ産生が著明に亢進していることを明らかにした。さらに,E-selectin ligand陽性細胞群ではHTLV-I proviral loadがE-selectin ligand陰性細胞群に比較して有意に高いことを明かにした。以上の事実よりHAM患者でのTh1へのimmune deviationは血管内皮細胞との接着における最初のステップであるrollingにおいて重要な役割を果たしているE-selectin ligand陽性CD陽性Tリンパ球の増加に起因し,E-selectin ligandの発現にはHTLV-I感染が強く関与していることが示された(論文投稿中)。 2,HAM患者末梢血CD4陽性Tリンパ球の機能検索 (1)VCAM-1/VLA-4pathwayを介してのmatrix metalloproteinase-2の発現亢進を明かにした(J Neuroimmunol99:242-247,1999)。 (2)HAM患者末梢血CD4陽性Tリンパ球ではFas抗原の発現亢進と共にapoptosis抑制系の蛋白であるBcl-xLの発現も亢進していてFas/Fas ligandを介したapoptosisに抵抗性を持ち,そのことが中枢神経系の慢性炎症に強く関与していることを示した(論文投稿中)。 3,HAM患者血清・髄液におけるTh1関連(IL-12,IFN-γ)およびTh2関連(IL-4,IL-10)サイトカインの検索HAM患者では対照群(HTLV-I seropositiveおよびseronegative control)に比較してTh1関連サイトカインは有意に高値であることを明らかにした(JNeuroimmunol95:185-189,1999)。 4,HAMに対する治療におけるTh1およびTh2関連サイトカインの動態の検索 pentoxifylline療法の前後で血清中Th1/Th2関連サイトカインを検索した結果,その治療が有効な症例ではTh2サイトカインが上昇してくることが明らかにされた(Intern Med38:717-721,1999)。以上のように,HAM患者末梢血Tリンパ球ではHTLV-Iのhigh proviral loadを基盤としてTh1/Th2バランスが極端にTh1に偏り(Med Hypotheses,in press),そのことがHAMの病態に強く関与していることが示された。

Research Products

(16 results)

All Other

All Publications (16 results)

[Publications] Masahiro Izumi,et al: "Sjogren's syndrome (SS) in patients with human T cell leukemia virus I associated myelopathy :paradoxical features of the major salivary glands compared to classical SS"J Rheumatol. 26. 2609-2614 (1999)
[Publications] Hideki Nakamura,et al: "Expression of mitogen-activated protein kinases in labial Salivary glands of patients with Sjogren's syndrome"Ann Rheumatic Dis. 58. 382-385 (1999)
[Publications] Hideki Nakamura,et al: "Expression of CD40/CD40 ligand and Bcl-2 family proteins in labial salivary glands of patients with Sjogren's syndrome"Lab Invest. 79. 261-269 (1999)
[Publications] Takafumi Furuya,et al: "Elevated levels of Interleukin-12 and Interferon-gamma in patients with human T lymphotropic virus type I-associated myelopathy"J Neuroimmunol. 95. 185-189 (1999)
[Publications] Yoko Nakao,et al: "Specificity of ω-conotoxin MVIIC binding and blocking calcium channel antibodies in Lambert-Eaton myasthenic syndrome"J Neurol. 246. 38-44 (1999)
[Publications] Izumi Horiuchi,et al: "Heightened IgE response to mite antigens in inflammatory neuropathies"J Neurol Sci. 166. 77-80 (1999)
[Publications] Masahiro Tominaga,et al: "Expression of metalloproteinase-2 ( gelatinase A) in labial salivary glands of Sjogren's syndrome with HTLV-I infection"Clin Exp Rheumatol. 17. 463-466 (1999)
[Publications] Takeshi Fujimoto,et al: "Relationship between the clinical efficacy of pentoxifylline treatment and elevation of serum Th2 cytokine levels in patients with HTLV-I-associated myelopathy"Intern Med. 38. 717-721 (1999)
[Publications] Chiaki Kambara,et al: "Vascular cell adhesion molecule-1-mediated matrix metalloproteinase-2 induction in peripheral blood T cells is up-regulated in patients with HTLV-I-associated myelopathy"J Neuroimmunol. 99. 242-247 (1999)
[Publications] Tatsutumi Nakamura,et al: "Importance of immune deviation toward Th1 in the early immunopathogenesis of human T-lymphotropic virus type I-associated myelopathy"Med Hypothese. (in press). (2000)
[Publications] Hideki Nakamura,et al: "Relationship between Sjogren's syndrome and HTLV-I infection : follow-up study of 83 patients"J Lab Clin Med. (in press). (2000)
[Publications] Shunya Nakane,et al.: "Comparative Molecular Analysis of HTLV-I Proviral DNA in HTLV-I Infected Members of a Family with a Discordant HTLV-I-Associated Myelopathy in Monozygotic Twins"J Neuro Virol. (in press). (2000)
[Publications] 中村龍文他: "Fas/Fas ligandと免疫性神経疾患"脳の科学. 5 (1999)
[Publications] 中村龍文: "重症筋無力症-その病態と臨床-"医学のあゆみ別冊「神経疾患-state of arts」. 3 (1999)
[Publications] 中村龍文: "免疫学からみた神経系と神経疾患"日本医学館. 8 (1999)
[Publications] 本村政勝他: "免疫学からみた神経系と神経疾患"日本医学館. 9 (1999)

1999 Fiscal Year Annual Research Report

Th1/Th2バランスからみたHAM発症分子機構の解明と治療法開発の基礎的検討

Principal Investigator

中村 龍文 長崎大学, 医学部・附属病院, 講師 (00198219)

Research Products

[Publications] Masahiro Izumi,et al: "Sjogren's syndrome (SS) in patients with human T cell leukemia virus I associated myelopathy :paradoxical features of the major salivary glands compared to classical SS"J Rheumatol. 26. 2609-2614 (1999)

[Publications] Hideki Nakamura,et al: "Expression of mitogen-activated protein kinases in labial Salivary glands of patients with Sjogren's syndrome"Ann Rheumatic Dis. 58. 382-385 (1999)

[Publications] Hideki Nakamura,et al: "Expression of CD40/CD40 ligand and Bcl-2 family proteins in labial salivary glands of patients with Sjogren's syndrome"Lab Invest. 79. 261-269 (1999)

[Publications] Takafumi Furuya,et al: "Elevated levels of Interleukin-12 and Interferon-gamma in patients with human T lymphotropic virus type I-associated myelopathy"J Neuroimmunol. 95. 185-189 (1999)

[Publications] Yoko Nakao,et al: "Specificity of ω-conotoxin MVIIC binding and blocking calcium channel antibodies in Lambert-Eaton myasthenic syndrome"J Neurol. 246. 38-44 (1999)

[Publications] Izumi Horiuchi,et al: "Heightened IgE response to mite antigens in inflammatory neuropathies"J Neurol Sci. 166. 77-80 (1999)

[Publications] Masahiro Tominaga,et al: "Expression of metalloproteinase-2 ( gelatinase A) in labial salivary glands of Sjogren's syndrome with HTLV-I infection"Clin Exp Rheumatol. 17. 463-466 (1999)

[Publications] Takeshi Fujimoto,et al: "Relationship between the clinical efficacy of pentoxifylline treatment and elevation of serum Th2 cytokine levels in patients with HTLV-I-associated myelopathy"Intern Med. 38. 717-721 (1999)

[Publications] Chiaki Kambara,et al: "Vascular cell adhesion molecule-1-mediated matrix metalloproteinase-2 induction in peripheral blood T cells is up-regulated in patients with HTLV-I-associated myelopathy"J Neuroimmunol. 99. 242-247 (1999)

[Publications] Tatsutumi Nakamura,et al: "Importance of immune deviation toward Th1 in the early immunopathogenesis of human T-lymphotropic virus type I-associated myelopathy"Med Hypothese. (in press). (2000)

[Publications] Hideki Nakamura,et al: "Relationship between Sjogren's syndrome and HTLV-I infection : follow-up study of 83 patients"J Lab Clin Med. (in press). (2000)

[Publications] Shunya Nakane,et al.: "Comparative Molecular Analysis of HTLV-I Proviral DNA in HTLV-I Infected Members of a Family with a Discordant HTLV-I-Associated Myelopathy in Monozygotic Twins"J Neuro Virol. (in press). (2000)

[Publications] 中村龍文 他: "Fas/Fas ligandと免疫性神経疾患"脳の科学. 5 (1999)

[Publications] 中村龍文: "重症筋無力症-その病態と臨床-"医学のあゆみ別冊「神経疾患-state of arts」. 3 (1999)

[Publications] 中村龍文: "免疫学からみた神経系と神経疾患"日本医学館. 8 (1999)

[Publications] 本村政勝他: "免疫学からみた神経系と神経疾患"日本医学館. 9 (1999)

中村龍文長崎大学, 医学部・附属病院, 講師 (00198219)

[Publications] 中村龍文他: "Fas/Fas ligandと免疫性神経疾患"脳の科学. 5 (1999)