2003 年度実績報告書

免疫学的機序が関与する消化器疾患の病態解明に関する研究

研究課題

研究課題/領域番号	15209024
研究種目	基盤研究(A)
研究機関	京都大学
研究代表者	千葉勉京都大学, 医学研究科, 教授 (30188487)
研究分担者	西尾彰功京都大学, 医学研究科, 助教授 (50362463) 岡崎和一関西医科大学, 内科学第三講座, 教授 (70145126)
キーワード	H.pylori / 胃炎 / 胃癌 / INF_γ / IL4 / MALTリンパ腫 / bFGF / 炎症性腸疾患
研究概要	1.H.pylori感染から胃癌へ至る過程における胃免疫反応について検討した。その結果、H.pylori感染胃粘膜にはCD4T細胞が著明に浸潤していた。またT細胞のサイトカイン産生を見ると、IL4産生に比してIFN_γ産生が約1000倍高値で、また血中の抗H.pylori抗体もIgG2が最も高値を示した。さらに胃潰瘍、十二指腸潰瘍、MALTリンパ腫患者について、その浸潤T細胞の性状を検討したところ、胃潰瘍患者のT細胞が最もTh1優位となっており、逆にMALTリンパ腫患者では著明なTh2へのシフトが観察された。以上より、胃潰瘍、粘膜萎縮、胃癌への過程にはTh1反応が強く関与し、逆にMALTリンパ腫の発症にはTh2反応が重要であると考えられた。 2.様々なマウスにH.pylori感染実験をおこなった。その結果、胃炎はC57Black, B6, Balb/cマウスの順に著明であった。さらにC57BlackマウスにEnteric helminthを感染させたところ、胃炎は著明に抑制された。また_γδT細胞欠損、IFN_γ欠損マウスにおいても胃炎は抑制された。さらにIFN_γ欠損マウスではIL7の発現が著明に低下し、一方正常マウスに抗IL7受容体抗体を投与すると_γδT細胞の浸潤が抑制され、同時に胃炎も改善した。以上よりH.pylori胃炎の進展にはTh1反応、それによる_γδT細胞の動員が必須であることが判明した。 3.炎症性腸疾患における、上皮Barrierの役割を明らかにする目的で、DSS腸炎マウスに、bFGFを投与して、腸炎に及ぼす影響を検討した。その結果bFGF投与マウスにおいては、大腸上皮の構築が維持されると同時に、腸粘膜の炎症細胞浸潤、サイトカイン産生、さらに腸内細菌に対する抗体産生が著明に抑制された。

研究成果
(16件)

すべてその他

すべて文献書誌 (16件)

[文献書誌] Watanabe N, Chiba T, et al.: "Spontaneous regression of Epstein-Barr virus-associated T-cell lymphoma of the stomach"Gastrointest Endosc. 57. 414-417 (2003)
[文献書誌] Watanabe N, Chiba T, et al.: "Elimination of local macrophages in the intestine prevents chronic colitis in interleukin-10 deficient mice"Dig Dis Sci. 48. 408-414 (2003)
[文献書誌] Uchida K, Chiba T, et al.: "A case of chronic pancreatitis involving an autoimmune mechanism that extended to retroperitoneal fibrosis"Pancreas. 26. 92-94 (2003)
[文献書誌] Nishi T, Chiba T, et al.: "Involvement of myeloid dendritic cells in the development of gastric secondary lymphoid foliicles in Helicobacter pylori-infected BALB/c mice with neonatal thymectomy"Infect Immun. 71. 2153-2162 (2003)
[文献書誌] Ohana M, Chiba T, et al.: "Prevention of the development of autoimmune gastritis by Helicobacter pylori infectgion in neonatal thymectomised mice"Gut. 52. 1102-1110 (2003)
[文献書誌] Watanabe T, Chiba T, et al.: "A liver tolerates to a portal antigen by generating CD11c+cells which select regulatory CD4+T cells via apoptosis"Hepatology. 38. 403-412 (2003)
[文献書誌] Fujii S, Chiba T, et al.: "Usefulness of analysis of p53 alteration and observation of surface microstructure for diagnosis of ulcerative colitis-associated colorectal neoplasia"J Exp Clin Cancer Res. 22. 421-429 (2003)
[文献書誌] Itoh T, Chiba T, et al.: "A coordinated cytotoxic effect of IFN-γ and cross-reactive antibodies in the pathogenesis of Helicobacter pylori gastritis"Helicobacter. 8. 268-278 (2003)
[文献書誌] Watanabe T, Chiba T, et al.: "CD4 T cells for IgE response to a dietary antigen develop in the liver"J Allergy Clin Immunol 111:1375-1385:2003. 111. 1375-1385 (2003)
[文献書誌] Taniguchi T, Chiba T, et al.: "High prevalence of autoantibodies against carbonic anhydrase II and lactoferrin in type 1 diabetes : Concept of autoimmune exocrinopathy and endocrinopathy of the pancreas"Pancreas. 27. 26-30 (2003)
[文献書誌] Fukui T, Chiba T, et al.: "Immuno-genetic analysis of gastric MALT lymphoma-like lesions induced by Helicobacter pylori infection in neonatally thymectomized mice"Lab Invest. (in press). (2004)
[文献書誌] Fujii S, Chiba T, et al.: "Development of colonic neoplasia in p53 deficient mice with experimental coiitis induced by dextran sulfate sodium"Gut. (in press). (2004)
[文献書誌] Fujii S, Chiba T, et al.: "Efficacy of surveillance and molecular markers for detection of ulcerative colitis-associated colorectal neoplasia"J Gastroenterol. 38. 1117-1125 (2004)
[文献書誌] Okazaki K, Chiba T, et al.: "Interaction of Helicobacter pylori-induced follicular gastritis and autoimmune gastritis in BALB/c mice with post-thymectomy autoimmune gastritis"J Gastroenterol. 38. 1131-1137 (2004)
[文献書誌] Suzuki K, Chiba T, et al.: "Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut"Proc Nat Acad Sci USA. 101. 1981-1986 (2004)
[文献書誌] Iwano M, Chiba T, et al.: "Characteristics of gastric B cell lymphoma of mucosa-associated lymphoid tissue type involving multiple organs"J Gastroenterol. (in press). (2004)

2003 年度 実績報告書

免疫学的機序が関与する消化器疾患の病態解明に関する研究

研究代表者

千葉 勉 京都大学, 医学研究科, 教授 (30188487)

研究成果

[文献書誌] Watanabe N, Chiba T, et al.: "Spontaneous regression of Epstein-Barr virus-associated T-cell lymphoma of the stomach"Gastrointest Endosc. 57. 414-417 (2003)

[文献書誌] Watanabe N, Chiba T, et al.: "Elimination of local macrophages in the intestine prevents chronic colitis in interleukin-10 deficient mice"Dig Dis Sci. 48. 408-414 (2003)

[文献書誌] Uchida K, Chiba T, et al.: "A case of chronic pancreatitis involving an autoimmune mechanism that extended to retroperitoneal fibrosis"Pancreas. 26. 92-94 (2003)

[文献書誌] Nishi T, Chiba T, et al.: "Involvement of myeloid dendritic cells in the development of gastric secondary lymphoid foliicles in Helicobacter pylori-infected BALB/c mice with neonatal thymectomy"Infect Immun. 71. 2153-2162 (2003)

[文献書誌] Ohana M, Chiba T, et al.: "Prevention of the development of autoimmune gastritis by Helicobacter pylori infectgion in neonatal thymectomised mice"Gut. 52. 1102-1110 (2003)

[文献書誌] Watanabe T, Chiba T, et al.: "A liver tolerates to a portal antigen by generating CD11c+cells which select regulatory CD4+T cells via apoptosis"Hepatology. 38. 403-412 (2003)

[文献書誌] Fujii S, Chiba T, et al.: "Usefulness of analysis of p53 alteration and observation of surface microstructure for diagnosis of ulcerative colitis-associated colorectal neoplasia"J Exp Clin Cancer Res. 22. 421-429 (2003)

[文献書誌] Itoh T, Chiba T, et al.: "A coordinated cytotoxic effect of IFN-γ and cross-reactive antibodies in the pathogenesis of Helicobacter pylori gastritis"Helicobacter. 8. 268-278 (2003)

[文献書誌] Watanabe T, Chiba T, et al.: "CD4 T cells for IgE response to a dietary antigen develop in the liver"J Allergy Clin Immunol 111:1375-1385:2003. 111. 1375-1385 (2003)

[文献書誌] Taniguchi T, Chiba T, et al.: "High prevalence of autoantibodies against carbonic anhydrase II and lactoferrin in type 1 diabetes : Concept of autoimmune exocrinopathy and endocrinopathy of the pancreas"Pancreas. 27. 26-30 (2003)

[文献書誌] Fukui T, Chiba T, et al.: "Immuno-genetic analysis of gastric MALT lymphoma-like lesions induced by Helicobacter pylori infection in neonatally thymectomized mice"Lab Invest. (in press). (2004)

[文献書誌] Fujii S, Chiba T, et al.: "Development of colonic neoplasia in p53 deficient mice with experimental coiitis induced by dextran sulfate sodium"Gut. (in press). (2004)

[文献書誌] Fujii S, Chiba T, et al.: "Efficacy of surveillance and molecular markers for detection of ulcerative colitis-associated colorectal neoplasia"J Gastroenterol. 38. 1117-1125 (2004)

[文献書誌] Okazaki K, Chiba T, et al.: "Interaction of Helicobacter pylori-induced follicular gastritis and autoimmune gastritis in BALB/c mice with post-thymectomy autoimmune gastritis"J Gastroenterol. 38. 1131-1137 (2004)

[文献書誌] Suzuki K, Chiba T, et al.: "Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut"Proc Nat Acad Sci USA. 101. 1981-1986 (2004)

[文献書誌] Iwano M, Chiba T, et al.: "Characteristics of gastric B cell lymphoma of mucosa-associated lymphoid tissue type involving multiple organs"J Gastroenterol. (in press). (2004)

2003 年度実績報告書

千葉勉京都大学, 医学研究科, 教授 (30188487)