1997 Fiscal Year Annual Research Report

粘膜免疫における上皮細胞とγδ/δβT型細胞間インターネットの解明

Research Project

Project/Area Number	09307006
Research Category	Grant-in-Aid for Scientific Research (A)
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)	島岡要大阪大学, 医学部, 助手 (40281133) 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	粘膜細胞間イントラネット / IL-7 / IL-7R / γδT細胞 / 上皮細胞 / 粘膜免疫
Research Abstract	当研究グループでは粘膜免疫機構の一つの特徴として上皮細胞と粘膜系T細胞が構成する粘膜細胞間イントラ・インターネットがその誘導・制御に中心的役割を果たしていることを提唱している。その中でも特に粘膜系γδT細胞と上皮細胞の相互作用に注目して解析を進めている。例えば、前者の細胞ではIL-7Rを発現しており、IL-7のシグナルによりIL-2Rの発現誘導とそれに引き続くγδT細胞の増殖を認められる。さらに、上皮細胞がIL-7特異的mRNAを発現しており同サイトカイン産生能力があることが分かっている。つまり、粘膜系γδT細胞と上皮細胞間にはIL-7/IL-7Rを媒体とした粘膜細胞間イントラネットが存在することが示唆される。それを直接的に証明するためにIL-7^+とIL-7R^+マウス用いて粘膜免疫機構を解析すると、IL-7R^+マウスでは腸管上皮細胞層に高頻度で存在するγδT細胞がFACS法で全く認められなかった。さらにVγ4,Vγ7に代表される上皮細胞間γδT細胞に特徴的に発現しているTCRγ鎖特異的mRNAがRT-PCR法により全く検出できなかった。これらの結果はIL-7/IL-7Rのシグナルが粘膜系γδT細胞の発達と活性化に不可欠であることを強く示唆している。現在、分泌型IgA誘導系に対してIL-7Rを介した粘膜細胞間イントラネットの破綻が及ぼす影響について解析を進めている。IL-γ^+マウスの場合にはγδT細胞の極度な減少が認められるが、IL-7R^+の様な消失は認められない。故にVγ4,Vγ7特異的mRNAの発現も検出可能であった。IL-r^+の状況ではγδT細胞の発現しているIL-7Rに同レセプターを共有する新規もしくは既知のサイトカインが結合し同細胞の活性化、増殖に必要な最小限のシグナルを提供している。一つの可能性としてTSLPの作用が示唆されている。これらの結果を総合すると上皮細胞とγδT細胞間においてIL-7/IL-7Rを介して粘膜細胞間イントラネットが形成されていることを強く示唆している。

Research Products
(15 results)

All Other

All Publications (15 results)

[Publications] Kiyono,H et.al: "Mucosal IL-12 switches type 2 help to an oral vaccine containing cholera toxin as adjuvant to type help with secretory IgA responses." Journal of Experimental Medicine.185. 415-427 (1997)
[Publications] Kiyono,H et.al: "Mutants in the putative ADP-ribosy transferase cleft of cholera toxin lack diarrhoeagenisity but retain adjuvanticity." Journal of Experimental Medecine. 185. 1203-1210 (1997)
[Publications] Kiyono,H et.al: "A nontoxic mtant of cholera toxin elicits Th2-type responses for enhanced mucosal immurity." Proceeding National Academy of Sciences USA.94. 5267-5272 (1997)
[Publications] Kiyono,H et.al: "Oral immunization of PspA elicits protectivehumoral immunity from Streptococcus pneumoniae infcction." Infection amd Immunity. 65. 640-644 (1997)
[Publications] Kiyono,H et.al: "Oral immunization with simian immunodeficiency virus(SIV)p55 gag and cholera toxin(CT)elicits both mucosal IgA and systemic IgG immune responses in non-human primates." Journal of Immunology. 158. 5321-5329 (1997)
[Publications] Kiyono,H et.al: "Functional γδT lymphocyte defect associated with human immunodeficiency virus infection." Molecular Medicine.3. 60-71 (1997)
[Publications] Kiyono,H et.al: "CD4^+ Cell population mediates development of inflammatory bowel disease in T cell receptor α-chain deficient mice." Gastoroenterology. 112. 1876-1886 (1997)
[Publications] Kiyono,H et.al: "Respiratory immunity to a replication-deficient adenovirus 5(Ade 5)vector and to its transgene:segregation of T helper cell responses." Journal of Immunology. 59. 685-693 (1997)
[Publications] Kiyono,H et.al: "Molecular and cellular mechanisms for periodontal diseases:role of Th1 and Th2 type cytokines in induction of mucosal inflamation." Journal of Periodontal Research. 32. 115-119 (1997)
[Publications] Kiyono,H et.al: "An interleukin 7 internet for intestinal intraepithelial γδT cell development:Knockoout of ligand or receptor revral deifferences in the immunodeficient state." European Journal of Immunology. 27. 2123-2132 (1997)
[Publications] Kiyono,H et.al: "Cholera toxin reverses the T cell dysfunction in spontaneously hypertensive rats via the stimulation of Th2-type responses." American Journal of Physiology. 273. R1509-R1518 (1997)
[Publications] Kiyono,H et.al: "Bacterial imasion induces interleukin-7(IL-7)receptor expression in colonic epitjelial cell line.T84." European Journal of Immunology. 27. 3456-3460 (1997)
[Publications] Kiyono,H et.al: "Springer Seminor.Immunopathol." A T cell/B cell Epithelial cell internet for mucosal inflammation and immunity.Vol.18, 18 (1997)
[Publications] Kiyono,H et.al: "BioDrags." Mucosal immunization for enteric diseases Current practice and future prospects.Vol.7, 24 (1997)
[Publications] Kiyono,H et.al: "In:Vaccines:New Advances in Technologies and Applocations." Optimizing mucosal vaccines for Th1 and Th2 type responses:regulating mucosal IgA responses., 5 (1997)

1997 Fiscal Year Annual Research Report

粘膜免疫における上皮細胞とγδ/δβT型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] Kiyono,H et.al: "Mucosal IL-12 switches type 2 help to an oral vaccine containing cholera toxin as adjuvant to type help with secretory IgA responses." Journal of Experimental Medicine.185. 415-427 (1997)

[Publications] Kiyono,H et.al: "Mutants in the putative ADP-ribosy transferase cleft of cholera toxin lack diarrhoeagenisity but retain adjuvanticity." Journal of Experimental Medecine. 185. 1203-1210 (1997)

[Publications] Kiyono,H et.al: "A nontoxic mtant of cholera toxin elicits Th2-type responses for enhanced mucosal immurity." Proceeding National Academy of Sciences USA.94. 5267-5272 (1997)

[Publications] Kiyono,H et.al: "Oral immunization of PspA elicits protectivehumoral immunity from Streptococcus pneumoniae infcction." Infection amd Immunity. 65. 640-644 (1997)

[Publications] Kiyono,H et.al: "Oral immunization with simian immunodeficiency virus(SIV)p55 gag and cholera toxin(CT)elicits both mucosal IgA and systemic IgG immune responses in non-human primates." Journal of Immunology. 158. 5321-5329 (1997)

[Publications] Kiyono,H et.al: "Functional γδT lymphocyte defect associated with human immunodeficiency virus infection." Molecular Medicine.3. 60-71 (1997)

[Publications] Kiyono,H et.al: "CD4^+ Cell population mediates development of inflammatory bowel disease in T cell receptor α-chain deficient mice." Gastoroenterology. 112. 1876-1886 (1997)

[Publications] Kiyono,H et.al: "Respiratory immunity to a replication-deficient adenovirus 5(Ade 5)vector and to its transgene:segregation of T helper cell responses." Journal of Immunology. 59. 685-693 (1997)

[Publications] Kiyono,H et.al: "Molecular and cellular mechanisms for periodontal diseases:role of Th1 and Th2 type cytokines in induction of mucosal inflamation." Journal of Periodontal Research. 32. 115-119 (1997)

[Publications] Kiyono,H et.al: "An interleukin 7 internet for intestinal intraepithelial γδT cell development:Knockoout of ligand or receptor revral deifferences in the immunodeficient state." European Journal of Immunology. 27. 2123-2132 (1997)

[Publications] Kiyono,H et.al: "Cholera toxin reverses the T cell dysfunction in spontaneously hypertensive rats via the stimulation of Th2-type responses." American Journal of Physiology. 273. R1509-R1518 (1997)

[Publications] Kiyono,H et.al: "Bacterial imasion induces interleukin-7(IL-7)receptor expression in colonic epitjelial cell line.T84." European Journal of Immunology. 27. 3456-3460 (1997)

[Publications] Kiyono,H et.al: "Springer Seminor.Immunopathol." A T cell/B cell Epithelial cell internet for mucosal inflammation and immunity.Vol.18, 18 (1997)

[Publications] Kiyono,H et.al: "BioDrags." Mucosal immunization for enteric diseases Current practice and future prospects.Vol.7, 24 (1997)

[Publications] Kiyono,H et.al: "In:Vaccines:New Advances in Technologies and Applocations." Optimizing mucosal vaccines for Th1 and Th2 type responses:regulating mucosal IgA responses., 5 (1997)

清野宏大阪大学, 微生物病研究所, 教授 (10271032)