| Project/Area Number |
16590739
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
ISOGAI Susumu Tokyo Medical and Dental University, graduate school, assistant, 医学部附属病院, 助手 (70361722)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | asthma / T cells / macrophages / interferon gamma / allergy / cytokine / lung / 炎症 |
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| Research Abstract |
We have previously shown that adoptively transferred CD8^+γδ T cells decrease late allergic airway responses, airway eosinophilia, airway T_H2 cytokine expression and increase IFN-γ expression. We hypothesized that the effects of CD8^+γδ T cells were IFN-γ mediated. All Brown Norway (BN) rats were sensitized to OVA on day 1. Cervical lymph node CD8^+γδ T cells from sensitized animals were treated with antisense phosphorothioated oligodeoxynucleotide (ODN ; 5μmol/L) to inhibit IFN-γ synthesis or control ODN and 3.5 x 10^4 CD8^+γδ T cells were injected i.p. into sensitized recipients on day 13. Control OVA-sensitized rats were injected with PBS. All rats were challenged with aerosolized OVA on day 15 and lung resistance was monitored over an 8-hour period, after which bronchoalveolar lavage was performed. Control ODN treated γδ T cells decreased late airway responses (P<0.05) and eosinophilia in bronchoalveolar lavage (P=0.001) compared to PBS injected animals. There was a complete recovery of late airway responses (P<0.05) and a partial recovery of airway eosinophilia (P<0.05) in recipients of antisense ODN treated cells. These results indicate that CD8^+γδ T cells inhibit late airway responses and airway eosinophilia through the secretion of IFN-γ. We showed that the two actions of IFN-γ on the macrophage, to reduce cysteinyl leukotrienes synthesis and to enhance phagocytosis, are both anti-inflammatory and likely contribute to the reduction of airway inflammation and late responses by CD8^+γδ T cells. Perhaps defective or altered γδ T cell function may account for some forms of allergic asthma.
We also investigated the role of CD8+ T cells in airway remodeling. CD8^+ T cells in rats were depleted during the repeated antigen challenges by treating them with a CD8antibody. CD8^+ T cells showed inhibitory effects on airway remodeling in this model of chronic asthma.
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