Project/Area Number |
08670911
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pediatrics
|
Research Institution | KITASATO UNIVERSITY |
Principal Investigator |
NOMA Takeshi Kitasato University, School of Medicine Assistant Professor, 医学部, 講師 (60208387)
|
Co-Investigator(Kenkyū-buntansha) |
YATA Junichi Tokyo ikashika University School of Medicine Professor, 医学部, 教授 (60057502)
|
Project Period (FY) |
1996 – 1998
|
Project Status |
Completed (Fiscal Year 1998)
|
Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
|
Keywords | mature B Cell lines secreting Dermatophagoides farinae (Df)-specific IgE / IL-10 / G-CSF / IL-12 / outgrowing mite-sensitive bronchial asthma / Df-specific Th0 cell clones / apoptosis / RS virus infection / cytokine inbalance / high dose IL-12 induces Th2 or Th0 responses / ダニ抗原特異IgE産生リンパ腫 / 抑制T細胞因子 / IL-1 / IL-5 / Th0タイプ / Th2タイプ / ダニ特異的Tリンパ球クローン |
Research Abstract |
We investigated immunologic mechanisms for outgrowing mite-sensitive bronchial asthma. In order to disclose the regulatory mechanisms in production of antigen-specific IgE in human systems we successfully established lines secreting Dermatophagoides farinae (Df) -specific IgE from peripheral mononuclear cells extracted from a patient with mite-sensitive asthma by immortalization with the Epstein-Barr virus. To advance the studies, we investigated (1) Immunologic mechanisms in onset of allergic deseases, (2) Natural outgrowing bronchial asthma, (3) Immunopharmacologic mechanisms of anti-allergic agents and relationships with the outgrowing bronchial asthma, and then (4) established human B cell lines secreting Dermatophagoides farinae-specific IgE and analyzed its regulatory mechanisms by inflammatory cytokines and soluble factors derived from T cell clones in patients with bronchial asthma in remission : it is likely that IL 10 triggers positive feedback mechanism in the IgE production in patients with bronchial asthma, resulting in the prolongation of asthmatic attack ; granulocyte-colony stimulating factor (G-CSF) augments the Df-specific IgE production by the activated mature B cells on stimulation of CD40 molecules, and assists IL-4, IL-13 or growth hormone (GH) function to increase the IgE production. JFN-γ or a low, but not a high, dose of IL-12 regulates these increased activities of the IgE ; The balance of apoptotic cell induction and IgE augmentation in mature B cells secreting Df-specific IgE by Df-specific T cell clones was likely involved in the clinical conditions in mite-sensitive asthma patients in remission. The factor (s) inducing apoptosis could contribute to treatment of bronchial asthma. We believe that outcomes of our study result in curative treatment of bronchial asthma.
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