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Molecular and immmunological analyses of cytokines and γδT cells in intracellular infection of Salmonella

Research Project

Project/Area Number 10470179
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

HARA Toshio  Kyushu University, Pediatrics, Professor, 大学院・医学系研究科, 教授 (40150445)

Co-Investigator(Kenkyū-buntansha) IHARA kenji  Kyushu University, Pediatrics, Teaching Stuff, 大学院・医学系研究科, 助手 (80294932)
TAKADA Hidetoshi  Kyushu University, Pediatrics, Teaching Stuff, 大学院・医学系研究科, 助手 (70294931)
OHGA Shouichi  Kyushu University, Pediatrics, Assistant Professor, 医学部, 助手(併任講師) (60233053)
NOMURA Akihiko  Kyushu University, Pediatrics, Senior Resident, 医学部, 医員
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥4,400,000 (Direct Cost: ¥4,400,000)
KeywordsγδT cell / intracellular bacteria / Salmonella / Interferonγ / Interleukin-12 / Interleukin-15 / Interleukn-18 / サルモネラ感染症 / 細胞内サイトカイン / IL-4 / IFN-γ / IL-12 / IL-15 / IL-18
Research Abstract

Abstract
Knowledge of the host immune response against Salmonella is not sufficient in humans. In the present study, Th1- and Th-1 including cytokines and T cell response were investigated in salmonellosis.
Serum Th-1 and Th-1including cytokine levels at acute phase in patients with salmonellosis were elevated. In addition, serum levels of IL-15 and IL-18 in patients with systematic form of salmonellosis were significantly higher than those in patients gastroenteritis form. By serial determination, serum IFN-γ ,IL-12, IL-15 and IL-18 levels in gastroenteritis form returned to normal levels easier than those in systematic form.
IFN-γ level was significantly correlated with IL-12 and IL-18 levels. In addition, IL-15 level was significantly correlated with IL-18 level. Furthermore, IFN-γ , IL-15 and IL-18 levels were significantly correlated with duration with fever.
Upon stimulation with Salmonella in vitro, IL-15 and IL-18 were produced by Salmonella, BCG or E. coli stimulation in both salmonellosis and controls, while IL-12 and IFN-γ were preferentially produced upon stimulation with Salmonella in Salmonellosis. A significant inhibition of Salmonella -induced IFN-γ production by anti-IL-12 mAb or anti-IL-18 mAb but not by anti-IL 15 mAb.
HLA-DR+T cells, CD69+T cells, γδT cells and HLA-DR+γδT cells were significantly elevated in systematic form than in gastroenteritis from. HLA-DR+T cell-number tended to correlate with serum IFN-γ, IL-15 and IL-18 levels. HLA-DR+γδT cell-number was marginally associated with IL-15 levels. Sorted γδT cells contained significantly higher levels of IFN-γ mRNA than αβT cells both in systemic and gastroenteritis forms
In summary, IL-12, IL-18, and IL-15, with complex mutual interactions , appear to be involved in total T cell activation as well as γδT cell-expansion, resulting in IFN- production for the protection against Salmonella infection in humans.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] 原 寿郎: "ヒトγδT細胞の基礎と臨床"日小血会誌. 12. 2-10 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toyoshima , et al.: "Ataxia-telangiectasia without immunodeficiency: Novel point mutations within and adjecent to the phoshatiatidylinositol 3-kinase-like domain."Am J Med Genet. 75. 141-144 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kira, et al.: "Nonsense mutation in exon 4 of human complement C9 gene is the major cause of Japanese complement C9 deficiency."Hum Genet. 102. 605-610 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takada, et al.: "Oversecretion of interleukin 18 in hemophagocylic lymphohistiocytosis: a novel new marker of disease activity."Br. J. Hematol. 106. 182-189 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Honda, et al.: "Thymus-independent expansion of T lymphocytes in children after allogeneic bone marrow transplantation."Bone Marrow Transplant. (発表予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Honda, et al.: "Measles virus-specific T helper 1/T helper 2-cytokine production in subacute sclerosing panencephalitis"J. NeuroVirology. (発表予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 原 寿郎: "生体防御とγδT細胞"小児科学年鑑. 4 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohga s, Kimura N, Takada H, Nagano M, Ohshimn K, Nomura A, Muraoka M, Take H, Yamamori S, Hata T.: "Restricted diversification of T-cells in chronic active Epstein-Barr virus infection : Potential inclination to T-lymphoproliferactive disease"Am. J. Hematol.. 61. 26-33 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishii E, Yoshida N, Kimura N, Fujimoto J, Mizutani S, Sano M, Hibi S, Nagano M, Yoshida T, Mori T, Kiyokawa N, Mohri S, Miyazaki S, Hara T.: "Clonal Dissemination of T lymphocytes in acid mice from familial hemophagocytic lymphohistiocytosis"Med Pediatr Oncol. 32. 201-208 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishii E, Kimura N, Kato K, Sato M, Nagano M. Nakagawa A, Okamura T, Yamaguchi H, Kawa. Hata Y.: "Clonal change of infiltrating T cells in children with familial hemophagocytic lymphohistiocytosis : possible association with Epstein-Barr virus infection"Cancer. 85. 1636-1643 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nagano M, Kimura N, Ishii E, Yoshida N, Yoshida T, Sako M, Hibi S, Imashuku S, Miyazaki S, Hata T, Mizutani S.: "Clonal expansion of ab-T lymphocytes with inverted Jb1 bias in familial hemophagocytic lymphohistiocytosis"Blood. 94. 2374-2382 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takabayashi A, Ihara K, Sasaki Y, Kusuhara K, Nishima S. Hata T.: "Novel polymorphism in the 5'-untranslated region of the interleukin-4 gene"J Hum Genet. 44. 352-353 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohga S, Okada K, Ueda K, Takada H, Ohta M, Aoki T, Kinuwaka N. Miyazaki S, Hata T.: "Cerebrospinal fluid cytokine levels and dexamethasone therapy in bacterial meningitis"J Infect. 39. 55-60 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ihara K, Ishii E, Eguchi M, Takada H, Suminoe A, Hata T.: "Identification of mutations in c-mpl gene in congential amegakaryocytic thrombocytopenia"Proc Natl Acad Sci USA. 96. 3132-3136 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kira R, Ihara K, Watanabe K, Kanemitsu S, Ahmed S, Gondo K, Takeshita, Hata T.: "Molecular epidemiology of C9 deficiency heterozygotes with an Arg95Stop mutation of C9 gene in Japan"J Hum Genet. 44. 109-111 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mitsuyasu H, Yanagihara Y, Mao X-Q, Gao P-S, Arinobu Y, Ihara K, Takabayashi A, Harat T, Enomoto T, Sasaki S, Kawai M, Hamasaki N, Shirakawa T, Hopkin JM, Izuhara K.: "Dominant effect of Ile50Val variant of the human interleukin-4 receptor a chain in IgE synthesis"J Immunol. 162. 1227-1231 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Aknemitsu S, Takabayashi A, Sasaki Y, Kuromaru R, Ihara K, Kaku Y, Sakai K, Hata T.: "Association of interleukin-4 receptor and interleukin-4 promoter gene polymorphisms with systematic lupus erythematosus"Arthritis & Rheumatism. 42. 1298-1300 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takada H, Ohga S, Mizuno Y, Sumonoe A, Matsuzaki A, Ihara K, Kinukawa N, Ohshima K, Kohno K, Kurimoto M, Hata T.: "Overexpression of IL-18 in haemmophagocytic lymphohistiocytosis : a novelmarker if disease activity"Br J Haemotol. 106. 182-189 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishii E, Zaitsu M, Ihara K, Hara T, Miyazaki S.: "High expression but no internal tandem duplication of FLT3 in normal hematopoietic cells"Pediatr Hematol Oncol. 16. 437-441 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohga S, Takada H, Honda K, Inamura T, Gondo K, Ohshima K, Yamamoto M, Hara T.: "Central nervous system T-lymphoproliferactive disorder in chronic active Epstein-Barr virus infection"J Pediatr Hematol/Oncol. 21. 42-46 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 原 寿郎: "ヒトγδT細胞の基礎と臨床"日小血会誌. 12. 2-10 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Toyoshima, et al.: "Ataxia-telangiectasia without immunodeficiency: Novel point mutations within and adjacent to the phosphatidylinositol 3-kinase-like domain."Am J Med Genet. 75. 141-144 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kira, et al.: "Nonsense mutation in exon 4 of human complement C9 gene is the major cause of Japanese complement C9 deficiency."Hum Genet. 102. 605-610 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takada, et al.: "Oversccretion of interlcukin 18 in hemophagocytic lymphohistiocytosis: a novel new marker of disease activity."Br J Hematol. 106. 182-189 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Honda, et al.: "Thymus-independent expansion of T lymphocytes in children after allogencic bone marrow transplantation."Bone Marrow Transplant. (発表予定).

    • Related Report
      1999 Annual Research Report
  • [Publications] Hara, et al: "Measies virus-specific T helper 1/T helper 2-cytokine production in subacute sclerosing panencephalitis."J Neuro Virology. (発表予定).

    • Related Report
      1999 Annual Research Report
  • [Publications] 原 寿郎: "生体防御とγδT細胞"小児科学年鑑. 4 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Toyoshima M,Hara T,Zhang H, Yamamoto T,Akaboshi S, Nanba E,Ohno K,Hori N,Sato K,Takeshita K.: "Ataxia-telangiectasia without immunodeficiency: Novel point mutations within and adjacent to the phosphatidylinositol 3-kinase-like domain." American Journal of Medical Genetics. 75. 141-144 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kira R,Ihara K,Takada H,Gondo K,Hara T.: "Nonsense mutation in exon 4 of human complement C9 gene is the major cause of Japanese complement C9 deficiency." Human Genetics. 102. 605-610 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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