1999 Fiscal Year Annual Research Report

粘膜免疫における上皮細胞とγδ/αβT細胞間インターネットの解明

Research Project

Project/Area Number	09307006
Research Institution	Osaka University
Principal Investigator	清野宏大阪大学, 微生物病研究所, 教授 (10271032)
Co-Investigator(Kenkyū-buntansha)	山本正文日本大学, 松戸歯学部, 講師 (80210558) 廣井隆親大阪大学, 微生物病研究所, 助手 (80228824) 高橋一郎大阪大学, 微生物病研究所, 講師 (20206791)
Keywords	粘膜細胞間インターネット / 粘膜細胞間イントラネット / 粘膜免疫機構 / 粘膜誘導型寛容 / 経口免疫寛容 / 粘膜系γδT細胞 / TCRδ遺伝子欠損マウス / IL-10
Research Abstract	本研究計画では様々な病原微生物やアレルゲンの侵入門戸である粘膜免疫機構の基礎的解明を目的としている。特に、上皮細胞と粘膜系γδ/αβT細胞が構成する粘膜細胞間インター・イントラネットに注目して、その誘導・制御システムについて解析を進めている。粘膜免疫機構の一つの大きな特徴であるγδT細胞に関して、アレルギーの予防に不可欠である粘膜誘導型寛容(例:経口免疫寛容)誘導メカニズムヘの関与について検討を加えて、興味ある結果を得ている。経口免疫寛容は投与される抗原の量により高濃度(例:T細胞クローナル欠損/アナジー化)寛容と低濃度(例:抑制シグナル)寛容誘導系により惹起される事が示唆されている。粘膜系γδT細胞は低濃度寛容誘導系に深く関わっている。つまり、γδT細胞の発達が欠落しているTCRδ遺伝子欠損マウスでは低濃度誘導系による経口免疫寛容が誘導されていない。さらに、粘膜系γδT細胞がIL-10を介してその経口免疫寛容の誘導を制御している事をつきとめている。つまり、アレルゲンが取り込まれる粘膜面で高頻度で存在するγδT細胞がサイトカインを介して粘膜誘導型寛容をコントロールしているという事を強く示唆しており、粘膜免疫システムを駆使したアレルギー予防・治療へ向けて新情報を提供した。さらに、この様にユニークな粘膜系γδT細胞の発達の場として、また粘膜細胞間イントラネットの中枢としての上皮細胞を考えたとき、癌化細胞だけでなく、正常な上皮細胞株の樹立がその解明に必要となってくる。最近、我々は胎生15-16週齢のマウスの腸管上皮細胞によりフィブロネクティンなど結合組織支持システムを培養系に応用する事でC-2、C6と名称した細胞株を樹立する事に成功している。現在、その特徴を解析する目的でサイトケラチン、分泌成分(SC)、サイトカイン産生能などについて既存の癌化上皮細胞株と比較しながら、検討を進めている。既存の癌化上皮細胞株だけでなく、このC-2、C-6を併用した培養系を確立する事で粘膜系γδ/αβT細胞との粘膜細胞間イントラネットの分子・細胞レベルでのメカニズムの解明が期待される。

Research Products
(30 results)

All Other

All Publications (30 results)

[Publications] Kweon, M-N., Kiyono, H. et al.: "Mucosally-induced systemic T cell unresponsiveness to ovalbumin requires CD40L-CD40 interactions"J. Immunol.. 162. 1904-1909 (1999)
[Publications] Fujihashi, K., Kiyono, H. et al.: "γδT cells are not essential for oral tolerance induced by large dose of ovalbumin, while regulate IL-10-mediated small dose systemic unresponsiveness"Int. Immunol.. 11. 1907-1916 (1999)
[Publications] Hiroi, T., Kiyono, H. et al.: "Deficiency of IL-5 receptorαchain selectively influences on the development of the commun mucosal immune system independent IgA producing B-1 cells in mucosal-associated tissues"J. Immunol.. 162. 821-828 (1999)
[Publications] Iijima, H., Kiyono, H. et al.: "Alteration of interleukin 4 production results in the inhibition of Th2 dominated inflammatory bowel disease in T cell receptor αchain-deficinet mice"J. Exp. Med.. 190. 607-616 (1999)
[Publications] Takahashi, I., Kiyono, H. et al.: "Clonal expansion of ββT cells in intestinal inflammatory resions of T cell receptor α-chain deficient mice"J. Immunol.. 162. 1843-1850 (1999)
[Publications] Yanagita, M., Kiyono, H. et al.: "Nasopharyngeal-associated lymphoreticular tissue (NALT) immunity : fimbriae-specific Th1 and Th2 cell-regulated IgA responses for the inhibition of bacterial attachment to epithelial cells and subsequent inflammatory cytokine"J. Immunol.. 162. 3559-3565 (1999)
[Publications] Dohi, T., Kiyono, H. et al.: "Hapten-induced colitis is associated with colonic patch hypertrophy and Th2 helper-type responses"J. Exp. Med.. 189. 1169-1179 (1999)
[Publications] Kurono, Y., Kiyono, H. et al.: "Nasal immunization induces Haemophilus influenzae-specific Th1 and Th2 responses with mucosal IgA and systemic IgG antibodies for protective immunity"J. Infect. Dise.. 180. 122-132 (1999)
[Publications] Boyaka, P. N., Kiyono, H. et al.: "Interleukin 12 is an effective adjuvant for induction of mucosal immunity"J. Immunol.. 162. 122-128 (1999)
[Publications] Marinaro, M., Kiyono, H. et al.: "Use of intranasal IL-12 to target predominantly Th1 responses to nasal and Th2 responses to oral vaccines given with cholera toxin"J. Immunol.. 162. 114-121 (1999)
[Publications] van Ginkel, F. W., Kiyono, H. et al.: "IgA-deficiency with increased Th2-Type cytokines in TgF-β1 knockout mice"J. Immunol.. 163. 1951-1957 (1999)
[Publications] Yamamoto, M., Kiyono, H. et al.: "Direct effects on antigen-presenting cells and T lymphocytes explain the adjuvanticity of a nontoxic cholera toxin mutant"J. Immunol.. 162. 7015-7021 (1999)
[Publications] Mbawuike, I.N., Kiyono, H. et al.: "IL-12 modulate IFN-γ synthesis and influenza-specific cytoxic activity by human CD45RO+ but not CD45RA, CD8+ T cells"J. Infect. Dis.. 180. 1477-1486 (1999)
[Publications] Pascual, D.W., Kiyono, H. et al.: "Extracellular expression of recombinant enterotoxigenic colonization factor antigen I by Salmonella elicits distinct T helper 2 followed by T helper 1cell responses"Infect. Immun.. 67. 6249-6256 (1999)
[Publications] McGhee, J.R., and Kiyono, H. et al.: "Mucosal Th1-versus Th2-type responses for antibody or cell mediated immunity to SIV rhesus macaques"J. Infect. Disc.. 179. 5480-5484 (1999)
[Publications] Tori, M., Kiyono, H. et al.: "Significant role of intragaft lymphoid tissues in preventing insulin-dependent diabetes mellitus recurrence in whole pancreaticoduodenal transplantation"Micro Surgery. 19. 338-343 (1999)
[Publications] Sugimoto, M., Kiyono, H. et al.: "Lymphocyte activation is attenuated by stellate ganglion block"Regional Anethesia and Pain Medicine. 24. 30-35 (1999)
[Publications] Tori, M., Kiyono, H. et al.: "IL-4 production in IDDM-nonrecurrent pancreas-transplanted BB rats with donor-derived NKR-P1+ TCRαβ+(NKT) cells but not in IDDM-recurrent BB rats"Transplanation Proceeding.. 31. 1940-1941 (1999)
[Publications] Host, D.F., Kiyono, H. et al.: "A double-blind, placebo-controlled study of Mycobacterium-specific human immune responses induced by intradermal bacille Calmette-Guerin vaccination"J. Lab. Clin. Med.. 134. 244-252 (1999)
[Publications] Saitoh-Inagawa, W., Kiyono, H. et al.: "Immunological characterization of lacrimal glands as a part of mucosal immune network"Invest. Ophthalmol. Visual Sci.. 41. 138-144 (2000)
[Publications] Higuchi, K., Kiyono, H. et al.: "Comparison of inhibitory effects of intranasal and oral administration of bovine type II collagen on collagen induced arthritis in DBA1/J mice"J. Rheumato.. (in press). (2000)
[Publications] Simeka, J.W., Kiyono, H. et al.: "Nasal immunization with protein and cholera toxin as adjuvant results in an IgE-associated inflammatory response in lugs"Infect. Immun.. (in press).
[Publications] McGhee, J.R. and Klyono, H.: "The Mucosal immune system. In : Fundamental Immunology 4th Edition, Paul, W.E.(ed)"Lippincott-Racen Press, Philadelphia.. 37 (1999)
[Publications] James, S.P. and Kiyono, H.: "Gastrointestinal and mucosal T cells. In : Mucosal Immunology, Ogra, P.L.et al. (eds)"Academic Press, San Diego.. 53 (1999)
[Publications] Hiroi, T., Kiyono, H. et al.: "IL-5R+, B-1 cells : Are they CMIS independent B cells for mucosal IgA plasma cells"Mucosal Immunol. Update. 3 (1999)
[Publications] Boyaka, P.N., Kiyono, H. et al.: "Strategies for mucosal vaccine development"Am. J. Trop. Med. Hyg.. 11 (1999)
[Publications] Takahashi, I., Kiyono, H. et al.: "Biochemical characterization of a population of CD4+, α-β+T cells in TCR-α mutant mice with inflammatory bowel diseases"FALK Proceeding. 5 (1999)
[Publications] Yamamoto, M. and Kiyono, H.: "Role of γδT cells in mucosal intranet."Allergol. Inten.. 5 (1999)
[Publications] Yamamoto, M. and Kiyono, H.: "Immunoregulatory functions of mucosal γδT cells"Microbes and Infection. 6 (1999)
[Publications] Takahashi, I. and Kiyono, H.: "Gut as the largest immunologic tissue"JPEN J. Parenter Enteral Nutr.. 6 (1999)

1999 Fiscal Year Annual Research Report

粘膜免疫における上皮細胞とγδ/αβT細胞間インターネットの解明

Principal Investigator

清野 宏 大阪大学, 微生物病研究所, 教授 (10271032)

Research Products

[Publications] Kweon, M-N., Kiyono, H. et al.: "Mucosally-induced systemic T cell unresponsiveness to ovalbumin requires CD40L-CD40 interactions"J. Immunol.. 162. 1904-1909 (1999)

[Publications] Fujihashi, K., Kiyono, H. et al.: "γδT cells are not essential for oral tolerance induced by large dose of ovalbumin, while regulate IL-10-mediated small dose systemic unresponsiveness"Int. Immunol.. 11. 1907-1916 (1999)

[Publications] Hiroi, T., Kiyono, H. et al.: "Deficiency of IL-5 receptorαchain selectively influences on the development of the commun mucosal immune system independent IgA producing B-1 cells in mucosal-associated tissues"J. Immunol.. 162. 821-828 (1999)

[Publications] Iijima, H., Kiyono, H. et al.: "Alteration of interleukin 4 production results in the inhibition of Th2 dominated inflammatory bowel disease in T cell receptor αchain-deficinet mice"J. Exp. Med.. 190. 607-616 (1999)

[Publications] Takahashi, I., Kiyono, H. et al.: "Clonal expansion of ββT cells in intestinal inflammatory resions of T cell receptor α-chain deficient mice"J. Immunol.. 162. 1843-1850 (1999)

[Publications] Dohi, T., Kiyono, H. et al.: "Hapten-induced colitis is associated with colonic patch hypertrophy and Th2 helper-type responses"J. Exp. Med.. 189. 1169-1179 (1999)

[Publications] Kurono, Y., Kiyono, H. et al.: "Nasal immunization induces Haemophilus influenzae-specific Th1 and Th2 responses with mucosal IgA and systemic IgG antibodies for protective immunity"J. Infect. Dise.. 180. 122-132 (1999)

[Publications] Boyaka, P. N., Kiyono, H. et al.: "Interleukin 12 is an effective adjuvant for induction of mucosal immunity"J. Immunol.. 162. 122-128 (1999)

[Publications] Marinaro, M., Kiyono, H. et al.: "Use of intranasal IL-12 to target predominantly Th1 responses to nasal and Th2 responses to oral vaccines given with cholera toxin"J. Immunol.. 162. 114-121 (1999)

[Publications] van Ginkel, F. W., Kiyono, H. et al.: "IgA-deficiency with increased Th2-Type cytokines in TgF-β1 knockout mice"J. Immunol.. 163. 1951-1957 (1999)

[Publications] Yamamoto, M., Kiyono, H. et al.: "Direct effects on antigen-presenting cells and T lymphocytes explain the adjuvanticity of a nontoxic cholera toxin mutant"J. Immunol.. 162. 7015-7021 (1999)

[Publications] Mbawuike, I.N., Kiyono, H. et al.: "IL-12 modulate IFN-γ synthesis and influenza-specific cytoxic activity by human CD45RO+ but not CD45RA, CD8+ T cells"J. Infect. Dis.. 180. 1477-1486 (1999)

[Publications] Pascual, D.W., Kiyono, H. et al.: "Extracellular expression of recombinant enterotoxigenic colonization factor antigen I by Salmonella elicits distinct T helper 2 followed by T helper 1cell responses"Infect. Immun.. 67. 6249-6256 (1999)

[Publications] McGhee, J.R., and Kiyono, H. et al.: "Mucosal Th1-versus Th2-type responses for antibody or cell mediated immunity to SIV rhesus macaques"J. Infect. Disc.. 179. 5480-5484 (1999)

[Publications] Tori, M., Kiyono, H. et al.: "Significant role of intragaft lymphoid tissues in preventing insulin-dependent diabetes mellitus recurrence in whole pancreaticoduodenal transplantation"Micro Surgery. 19. 338-343 (1999)

[Publications] Sugimoto, M., Kiyono, H. et al.: "Lymphocyte activation is attenuated by stellate ganglion block"Regional Anethesia and Pain Medicine. 24. 30-35 (1999)

[Publications] Tori, M., Kiyono, H. et al.: "IL-4 production in IDDM-nonrecurrent pancreas-transplanted BB rats with donor-derived NKR-P1+ TCRαβ+(NKT) cells but not in IDDM-recurrent BB rats"Transplanation Proceeding.. 31. 1940-1941 (1999)

[Publications] Host, D.F., Kiyono, H. et al.: "A double-blind, placebo-controlled study of Mycobacterium-specific human immune responses induced by intradermal bacille Calmette-Guerin vaccination"J. Lab. Clin. Med.. 134. 244-252 (1999)

[Publications] Saitoh-Inagawa, W., Kiyono, H. et al.: "Immunological characterization of lacrimal glands as a part of mucosal immune network"Invest. Ophthalmol. Visual Sci.. 41. 138-144 (2000)

[Publications] Higuchi, K., Kiyono, H. et al.: "Comparison of inhibitory effects of intranasal and oral administration of bovine type II collagen on collagen induced arthritis in DBA1/J mice"J. Rheumato.. (in press). (2000)

[Publications] Simeka, J.W., Kiyono, H. et al.: "Nasal immunization with protein and cholera toxin as adjuvant results in an IgE-associated inflammatory response in lugs"Infect. Immun.. (in press).

[Publications] McGhee, J.R. and Klyono, H.: "The Mucosal immune system. In : Fundamental Immunology 4th Edition, Paul, W.E.(ed)"Lippincott-Racen Press, Philadelphia.. 37 (1999)

[Publications] James, S.P. and Kiyono, H.: "Gastrointestinal and mucosal T cells. In : Mucosal Immunology, Ogra, P.L.et al. (eds)"Academic Press, San Diego.. 53 (1999)

[Publications] Hiroi, T., Kiyono, H. et al.: "IL-5R+, B-1 cells : Are they CMIS independent B cells for mucosal IgA plasma cells"Mucosal Immunol. Update. 3 (1999)

[Publications] Boyaka, P.N., Kiyono, H. et al.: "Strategies for mucosal vaccine development"Am. J. Trop. Med. Hyg.. 11 (1999)

[Publications] Takahashi, I., Kiyono, H. et al.: "Biochemical characterization of a population of CD4+, α-β+T cells in TCR-α mutant mice with inflammatory bowel diseases"FALK Proceeding. 5 (1999)

[Publications] Yamamoto, M. and Kiyono, H.: "Role of γδT cells in mucosal intranet."Allergol. Inten.. 5 (1999)

[Publications] Yamamoto, M. and Kiyono, H.: "Immunoregulatory functions of mucosal γδT cells"Microbes and Infection. 6 (1999)

[Publications] Takahashi, I. and Kiyono, H.: "Gut as the largest immunologic tissue"JPEN J. Parenter Enteral Nutr.. 6 (1999)

清野宏大阪大学, 微生物病研究所, 教授 (10271032)