| Project/Area Number |
07557030
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 試験 |
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| Research Field |
Immunology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TAKATSU Kiyoshi The University of Tokyo, Institute of Medical Science, Professor, 医科学研究所, 教授 (10107055)
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| Co-Investigator(Kenkyū-buntansha) |
UEHARA Shoji The University of Tokyo, Institute of Medical Science, Research associate, 医科学研究所, 教務職員 (60272499)
KARIYONE Ai The University of Tokyo, Institute of Medical Science, Research associate, 医科学研究所, 教務職員 (50114450)
KIKUCHI Yuji The University of Tokyo, Institute of Medical Science, Research associate, 医科学研究所, 助手 (60262078)
KINASHI Tatsuo The University of Tokyo, Institute of Medical Science, Research associate, 医科学研究所, 助手 (30202039)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 1996: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1995: ¥8,500,000 (Direct Cost: ¥8,500,000)
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| Keywords | late phase allergic response / eosinophils / IL-5 / IL-5Ralpha deficient mice / anti hIL-5R Ab / JAK / STAT path way / サイトカイン / IL-5欠損マウス / 広東住血線虫 / 気道過敏性 / 遅発型喘息 |
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| Research Abstract |
Interleukin-5 (IL-5) induces proliferation and differentiation of eosinophils by interacting with is receptor (IL-5R) which consists of two distinct polypeptide chains, alpha and beta (betac). In this project, IL-5 transgenic (IL-5-Tg) mice and IL-5R alpha deficient (IL-5Ralpha^<-/->) mice were employed to study the relative role of IL-5 in eosinophil-mediated inflamation. We also investigated the IL-5-mediated signals in human cells.
[Results]
1. IL-5-Tg mice actively sensitized with ovalbumin displayd more profound airway hyperreactivity in response to acetylcholine 24h after inhalation challenge with ovalbumin.
2. Stimulation of M.tuberculosis-primed lymph node cells with MPT59 induced proliferative response, production of IL-2 and IFNgamma, and the epression of Vbeta11^+CD4^+T cells in conjunction with antigen-presenting cells in an I-A^b-restricted manner.
3. Immunoprecipitation analysis using anti-hIL-5R mAb demonstrated that binding of hIL-5 to hIL-5Ralpha induced the recruitment of bc to hIL-5Ralpha together with hIL-5, although each subunit existed independently in the absence of IL-5.
4. Analysis of IL-5Ralpha^<-/-> mice revealed that IL-5 playd an obligatory role in development of B-1 cells and eosinophilopoiesis in vivo, and IL-5-induced eosinophils served as potent effector cells in killing of intracranial worms in mice.
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