1998 年度実績報告書

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

研究課題

研究課題/領域番号	09307006
研究種目	基盤研究(A)
研究機関	大阪大学
研究代表者	清野宏大阪大学, 微生物病研究所, 教授 (10271032)
研究分担者	島岡要大阪大学, 医学部, 助手 (40281133) 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)
キーワード	粘膜免疫 / 粘膜細胞間イントラネット / 上皮細胞間リンパ球 / パイエル板 / IgA / コレラ毒素
研究概要	本研究計画の目的は第一線の防御バリアーとして中心的役割を果たしている粘膜免疫機構を構成している上皮細胞、粘膜系αβT細胞とγδT細胞、Bα細胞による粘膜細胞間イントラ・インターネットの基礎的解明を推進することである。粘膜免疫システムの特徴である上皮細胞間リンパ球(IEL)にはαβT細胞だけでなく高頻度でγδT細胞が存在し隣在する上皮細胞との間にユニークな細胞間ネットワークを形成して粘膜免疫機構の一翼を担っている。我々は腸管という細菌をはじめとする無数の生物活性化分子・物質に常に曝されている環境下でIELに異常な免疫応答・細胞増殖を起こさせないメカニズムの解明を進めて来たが、最近興味ある結果を得た。マウスIEL由来のT細胞をTCRを介して活性化する培養系に同種マウスから精製分離した腸管上皮細胞を添加すると細胞増殖が顕著に抑制された。さらに上皮細胞の膜分画にIEL由来のαβT細胞とγδT細胞を選択的に抑制する活性があることを確認し、現在その分子の同定を進めている。また粘膜細胞間イントラネットを調節するタンパクとしてコレラ毒素(CT)が良くしられているがそのメカニズムについてはまだ未解明な部分が多い。そこで、我々はCTの粘膜免疫調節因子としての作用メカニズムを解明する目的でマウスをスーパー抗原であるSEBをCT存在、非存在下で経口免疫し、パイエル板T細胞への影響を検討した。その結果CTはSEBによって誘導されるVβ8T細胞群のクローン除去は阻止できないが、アナジー化の誘導を回避し、抗原特異的IgAやIgG抗体を誘導した。つまり、CTの粘膜アジュバント効果のなかには、T細胞のアナジー化を阻止する働きがあることが示唆された。

研究成果
(36件)

すべてその他

すべて文献書誌 (36件)

[文献書誌] Yamamoto,M.,Kiyono,H.et al: "Mucosal Intranet:intestinal epithelial cells down regulate intraepithelial but not peripheral T lymphocytes." J.Immunol.160. 2188-2196 (1998)
[文献書誌] Iijima,H.,Kiyono,H.et al: "Orally-administered cholera toxin rescues murine gastrointestinal T cells from staphylococcal enterotoxin B-induced anergy." Gastroenterology. 115. 1197-1204 (198)
[文献書誌] Kweon,M-N.,Kiyono,H.et al: "The role of Thl cells in tolerance:lack of mucosally-induced unresponsiveness in interferon-gamma knockout mice." J.Immunol.160. 1687-1696 (1998)
[文献書誌] Ithoh,M.,Kiyono,H.et al: "Deletion of BST-1(CD157)gene impaired systemic T1-2 antigen-induced IgG3 and mucosal TD antigen-elicited IgA responses." J.Immunol.161. 3974-3983 (1998)
[文献書誌] Hiroi,T.,Kiyono,H.et al: "Nasal immune system:Distinctive Th0 and Th1/Th2 type enviroments in murine nasal associated lymphoid tissues and nasal passage,respectively." Eur.J.Immunol.28. 3346-3353 (1998)
[文献書誌] Kawabata,S.,Kiyono,H,et al: "Unique characteristics of intraepithelial lymphocytes from villi tip and and cript portions of the small intestine." Gastroenterology. 115. 866-873 (1998)
[文献書誌] Yamamoto,M.,Kiyono,H. et al: "A nontoxic adjuvant for mucosal immunity to pneumucoccal surface protein A." J.Immunol.161. 4115-4121 (1998)
[文献書誌] Wikox,P.R.,Kiyono,H.et al: "High mucosal levels of tumor necrosis factor-α mRNA are associated with cytomegalovirus" Gastroenterology. 114. 77-82 (1998)
[文献書誌] Imaoka,K.,Kiyono,H.et al: "Nasal immunization of non-human primates with simian immunodeficiency virus p55gag and cholera toxin adjuvant induces Th1/Th2 help for anti-viral immunity." J.Immunol.161. 5952-5958 (1998)
[文献書誌] Lu,X.,Kiyono,H.et al: "Targeted lymph node immunization with whole-inactivated SIV or envelope and core subunit antigen vaccines does not reliably protect rhesus macaques from vaginal challenge with SIV" Gastroenterology. 114. 77-82 (1998)
[文献書誌] Kawabata,S.,Kiyono,H.et al: "Induction of polarized Th2 cytokine expression for p27-specific IgA B cell responses after immunnization with antigen in rhesus macaques." J.Infect.Dise.177. 26-33 (1998)
[文献書誌] Nguyen,H.H.,Kiyono,H.et al: "Influenza virus-infected epithelial cells present viral antigen to antigen-specific CD8+cytotoxic T lymphocytes(CTL)." J.Virology. 72. 4534-4536 (1998)
[文献書誌] Harris,P.R.,Kiyono,et al: "Rocombinant Helicobacter pylori urease activates primmary mucosal macrophages." J.Infect.Dis.178(5). 1516-1520 (1998)
[文献書誌] Yuki,Y.,Kiyono,H.et al: "Human milk proteins including secretory IgA fail to elicit tolerance after feeding." Intern Immunol.10. 537-545 (1998)
[文献書誌] Sugimoto,M.,Kiyono,H.et al: "Upregulation of fas ligand(Fas L)mRNA expression in peripheral blood mononuclear cells(PBMC)after major surgery." Clin.Exp.Immunol.112. 120-125 (1998)
[文献書誌] Shimaoka,M.,Kiyono,H.et al: "High frequency oscillatory ventilation attenuates the activation of alveolar macrophages and neutrophils in lung injury." Crit.Care. 2. 35-39 (1998)
[文献書誌] Salbi,G.E.,Kiyono,H.et al: "Inflammatory mediators of the terminal dentition in adult and early onset periodontitis." J.Periodontal Res.33. 212-215 (1998)
[文献書誌] Shimaoka,M.,Kiyono,H.et al: "The influence of surgical stress on T cells:enhancement of early phase lymphocyte activation." Aneth.Analg.87. 1431-1435 (1998)
[文献書誌] VanCott,J.L.,Kiyono,H.et al: "Regualtion of host immune responses by modification of Salmonella virulence gene." Nature Medicine.4. 1247-1252 (1998)
[文献書誌] Takahashi,I.,Kiyono,H.: "γδT cells:Bodyguards and/or sleepers in the gut." Chemical Immunol.71. 77-87 (1998)
[文献書誌] Boyaka,P.N.,Kiyono,H.et al: "Interleukin 12 is an effective adjuvant for induction of mucosal immunity." J.Immunol.162. 122-128 (1998)
[文献書誌] Marinaro,M.,Kiyono,H.et al: "Use of intranasal IL-12 to target predominatly Th1 responses to nasal and Th2 responses to oral vaccines given with cholera toxin." J.Immunol.162. 114-121 (1998)
[文献書誌] Hiroi,T.,Kiyono,H.et al: "Deficiency of IL-5 receptor α chain selectively influences on the development of the comman mucosal immune system independent IgA producing B-1 cells in mucosal-associated tissues." J.Immunol.162. 821-828 (1999)
[文献書誌] Takahashi,I.,Kiyono,H.et al: "Clonal expansion of CD4^+TCR_<ββ>^+T cells in T cell receptor α-chain deficient mice by gutderived antigens." J.Immunol.162. 1843-1850 (1999)
[文献書誌] Kweon,M-N.,Kiyono,H.et al: "Mucosally-induced systemic T cell unresponsiveness to ovalbumin requires CD40L-CD40 interactions." J.Immunol.(in press). (1999)
[文献書誌] Tori,M.,Kiyono,H.et al: "The significant role of intragraft lymphoid tissues in preventing IDDM(insulin-dependent diabetes mellitus)recurrence in whole pancreaticoduodenal transplantation." J.Micro Surgery.(in press). (1999)
[文献書誌] McGhee,J.R.,Kiyono,H.et al: "Mucosal Th1-versus Th2-type responses for antigody or cell mediated immunity to SIV rhesus macaques." J.Infect.Dise.(in press). (1999)
[文献書誌] Yanagita,M.,Kiyono,H.et al.: "Nasopharyngeal-associated lymphoreticular tissue(NALT)immunity:timbriae-specific Th1 and Th2 cell-cells and subsequent inflammatory cytokine production." J.Immunol.(in press). (1999)
[文献書誌] Kurono,Y.,Kiyono,H.et al: "Mucosal Solutions.Advances in Mucosal Immunology." SMI,Maryland, 311-315 (1998)
[文献書誌] McGhee,J.R.,Kiyono,H.et al: "Fundamental Immunology 4th Edition" Lippincott-Raven Press,Philadelphia, 909-945 (1999)
[文献書誌] VanCott,J.L.,Kiyono,H.et al: "Importance of vaccine delivery mode on outcome of helper T subsets and cytokines for IgA responses (in press)" Recent Advances in Otitis Media, (1999)
[文献書誌] Boyaka,P.N.,Kiyono,H.et al: "Strategies for mucosal vaccine development (in press)" Tropical Medicine, (1999)
[文献書誌] Takahashi,I.,Kiyono,H.: "Biochemical characterization of a population of CD4^+,α^-β^+T cells in TCR-α mutant mice with inflammatory bowel diseases" FALK Proceeding, 142-146 (1999)
[文献書誌] James,S.P.,Kiyono,H.: "Mucosal Immunology" Academic Press, 381-396 (1999)
[文献書誌] Yamamoto,M.,Kiyono,H.: "γδT cells in mucosal intranet. (in press)" Allergol.Intern., (1999)
[文献書誌] Yamamoto,M.,Kiyono,H.: "Immunoregulatory function of mucosal γδT cells (in press)" Annu.Inst.Pasture., (1999)

1998 年度 実績報告書

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

研究代表者

清野 宏 大阪大学, 微生物病研究所, 教授 (10271032)

研究成果

[文献書誌] Yamamoto,M.,Kiyono,H.et al: "Mucosal Intranet:intestinal epithelial cells down regulate intraepithelial but not peripheral T lymphocytes." J.Immunol.160. 2188-2196 (1998)

[文献書誌] Iijima,H.,Kiyono,H.et al: "Orally-administered cholera toxin rescues murine gastrointestinal T cells from staphylococcal enterotoxin B-induced anergy." Gastroenterology. 115. 1197-1204 (198)

[文献書誌] Kweon,M-N.,Kiyono,H.et al: "The role of Thl cells in tolerance:lack of mucosally-induced unresponsiveness in interferon-gamma knockout mice." J.Immunol.160. 1687-1696 (1998)

[文献書誌] Ithoh,M.,Kiyono,H.et al: "Deletion of BST-1(CD157)gene impaired systemic T1-2 antigen-induced IgG3 and mucosal TD antigen-elicited IgA responses." J.Immunol.161. 3974-3983 (1998)

[文献書誌] Hiroi,T.,Kiyono,H.et al: "Nasal immune system:Distinctive Th0 and Th1/Th2 type enviroments in murine nasal associated lymphoid tissues and nasal passage,respectively." Eur.J.Immunol.28. 3346-3353 (1998)

[文献書誌] Kawabata,S.,Kiyono,H,et al: "Unique characteristics of intraepithelial lymphocytes from villi tip and and cript portions of the small intestine." Gastroenterology. 115. 866-873 (1998)

[文献書誌] Yamamoto,M.,Kiyono,H. et al: "A nontoxic adjuvant for mucosal immunity to pneumucoccal surface protein A." J.Immunol.161. 4115-4121 (1998)

[文献書誌] Wikox,P.R.,Kiyono,H.et al: "High mucosal levels of tumor necrosis factor-α mRNA are associated with cytomegalovirus" Gastroenterology. 114. 77-82 (1998)

[文献書誌] Imaoka,K.,Kiyono,H.et al: "Nasal immunization of non-human primates with simian immunodeficiency virus p55gag and cholera toxin adjuvant induces Th1/Th2 help for anti-viral immunity." J.Immunol.161. 5952-5958 (1998)

[文献書誌] Lu,X.,Kiyono,H.et al: "Targeted lymph node immunization with whole-inactivated SIV or envelope and core subunit antigen vaccines does not reliably protect rhesus macaques from vaginal challenge with SIV" Gastroenterology. 114. 77-82 (1998)

[文献書誌] Kawabata,S.,Kiyono,H.et al: "Induction of polarized Th2 cytokine expression for p27-specific IgA B cell responses after immunnization with antigen in rhesus macaques." J.Infect.Dise.177. 26-33 (1998)

[文献書誌] Nguyen,H.H.,Kiyono,H.et al: "Influenza virus-infected epithelial cells present viral antigen to antigen-specific CD8+cytotoxic T lymphocytes(CTL)." J.Virology. 72. 4534-4536 (1998)

[文献書誌] Harris,P.R.,Kiyono,et al: "Rocombinant Helicobacter pylori urease activates primmary mucosal macrophages." J.Infect.Dis.178(5). 1516-1520 (1998)

[文献書誌] Yuki,Y.,Kiyono,H.et al: "Human milk proteins including secretory IgA fail to elicit tolerance after feeding." Intern Immunol.10. 537-545 (1998)

[文献書誌] Sugimoto,M.,Kiyono,H.et al: "Upregulation of fas ligand(Fas L)mRNA expression in peripheral blood mononuclear cells(PBMC)after major surgery." Clin.Exp.Immunol.112. 120-125 (1998)

[文献書誌] Shimaoka,M.,Kiyono,H.et al: "High frequency oscillatory ventilation attenuates the activation of alveolar macrophages and neutrophils in lung injury." Crit.Care. 2. 35-39 (1998)

[文献書誌] Salbi,G.E.,Kiyono,H.et al: "Inflammatory mediators of the terminal dentition in adult and early onset periodontitis." J.Periodontal Res.33. 212-215 (1998)

[文献書誌] Shimaoka,M.,Kiyono,H.et al: "The influence of surgical stress on T cells:enhancement of early phase lymphocyte activation." Aneth.Analg.87. 1431-1435 (1998)

[文献書誌] VanCott,J.L.,Kiyono,H.et al: "Regualtion of host immune responses by modification of Salmonella virulence gene." Nature Medicine.4. 1247-1252 (1998)

[文献書誌] Takahashi,I.,Kiyono,H.: "γδT cells:Bodyguards and/or sleepers in the gut." Chemical Immunol.71. 77-87 (1998)

[文献書誌] Boyaka,P.N.,Kiyono,H.et al: "Interleukin 12 is an effective adjuvant for induction of mucosal immunity." J.Immunol.162. 122-128 (1998)

[文献書誌] Marinaro,M.,Kiyono,H.et al: "Use of intranasal IL-12 to target predominatly Th1 responses to nasal and Th2 responses to oral vaccines given with cholera toxin." J.Immunol.162. 114-121 (1998)

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

[文献書誌] Takahashi,I.,Kiyono,H.et al: "Clonal expansion of CD4^+TCR_<ββ>^+T cells in T cell receptor α-chain deficient mice by gutderived antigens." J.Immunol.162. 1843-1850 (1999)

[文献書誌] Kweon,M-N.,Kiyono,H.et al: "Mucosally-induced systemic T cell unresponsiveness to ovalbumin requires CD40L-CD40 interactions." J.Immunol.(in press). (1999)

[文献書誌] Tori,M.,Kiyono,H.et al: "The significant role of intragraft lymphoid tissues in preventing IDDM(insulin-dependent diabetes mellitus)recurrence in whole pancreaticoduodenal transplantation." J.Micro Surgery.(in press). (1999)

[文献書誌] McGhee,J.R.,Kiyono,H.et al: "Mucosal Th1-versus Th2-type responses for antigody or cell mediated immunity to SIV rhesus macaques." J.Infect.Dise.(in press). (1999)

[文献書誌] Yanagita,M.,Kiyono,H.et al.: "Nasopharyngeal-associated lymphoreticular tissue(NALT)immunity:timbriae-specific Th1 and Th2 cell-cells and subsequent inflammatory cytokine production." J.Immunol.(in press). (1999)

[文献書誌] Kurono,Y.,Kiyono,H.et al: "Mucosal Solutions.Advances in Mucosal Immunology." SMI,Maryland, 311-315 (1998)

[文献書誌] McGhee,J.R.,Kiyono,H.et al: "Fundamental Immunology 4th Edition" Lippincott-Raven Press,Philadelphia, 909-945 (1999)

[文献書誌] VanCott,J.L.,Kiyono,H.et al: "Importance of vaccine delivery mode on outcome of helper T subsets and cytokines for IgA responses (in press)" Recent Advances in Otitis Media, (1999)

[文献書誌] Boyaka,P.N.,Kiyono,H.et al: "Strategies for mucosal vaccine development (in press)" Tropical Medicine, (1999)

[文献書誌] Takahashi,I.,Kiyono,H.: "Biochemical characterization of a population of CD4^+,α^-β^+T cells in TCR-α mutant mice with inflammatory bowel diseases" FALK Proceeding, 142-146 (1999)

[文献書誌] James,S.P.,Kiyono,H.: "Mucosal Immunology" Academic Press, 381-396 (1999)

[文献書誌] Yamamoto,M.,Kiyono,H.: "γδT cells in mucosal intranet. (in press)" Allergol.Intern., (1999)

[文献書誌] Yamamoto,M.,Kiyono,H.: "Immunoregulatory function of mucosal γδT cells (in press)" Annu.Inst.Pasture., (1999)

1998 年度実績報告書

清野宏大阪大学, 微生物病研究所, 教授 (10271032)