| Project/Area Number |
11670560
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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 | Tohoku University |
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Principal Investigator |
SANO Kunio Tohoku Univ., medicine, Research Associate, 大学院・医学系研究科, 助手 (20192601)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | CpG / dendritic cells / Th1 / Th2 cells / TGF-β / bronchial asthma / allergy |
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| Research Abstract |
We investigated whether the induction of immune tolerance of Th2 cells could ameliorate bronchial asthma using a murine model of the disease. First, we analyzed the inhibition of Th2 cells by suppressor T cells. We found that high doses of antigen in the trachea could induce TGF-β-secreting CD4 T cells that inhibited airway eosinophilia. This result indicate that exposure to high doses of antigen did no result in the exacerbation of inflammatory responses in the airway, but rather avoid destructive inflammation by inducing immune tolerance through the activation of the regulatory CD4 T cells. The novel regulatory CD4 T cells secreting TGF-β could be used as a possible therapeutic tool, because the activation of the regulatory T cells would inhibit Th2 cells and the subsequent airway inflammation.
Another regulatory T cells are Th1 cells. Th1 cells inhibited Th2 cells efficiently when two types of T cells share the antigen specificity. We previous observed that strong Th1-inducing pathogen, Mycobacterium tuberculosis, could induce Ag-specific Th1 cells if the Ag was immunized together with the bacilli. To extend our observations, we introduced CpG ODN that had been reported to mimic the Th1-inducing activity of M. tuberculosis. Immunization with the mixture of CpG and Ag induced Th1 cells, and the conjugation of CpG and Ag enhanced CpG's effects by 100-fold. Anti-inflammatory effects of CpG on airway eosinophilic responses were also augmented by 100-fold when CpG was conjugated to the Ag. These effects were associated with the induction of Ag-specific Th2 cell tolerance in the regional lymph nodes. Interestingly, the effects of CpG-Ag conjugates as therapeutic reagents to bronchial asthma lasted at least for 8 weeks. These observations highlight the beneficial aspects of CpG-conjugated allergen as a possible promising vaccine to treat bronchial asthma.
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