2004 Fiscal Year Final Research Report Summary
Study of γδ T cells on the mechanism of bronchial asthma
| Project/Area Number |
13670457
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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 |
内科学一般
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
KANEHIRO Arihiko Okayama University, Okayama University Hospital, Assistant Professor, 医学部・歯学部附属病院, 助手 (20243503)
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| Project Period (FY) |
2001 – 2004
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| Keywords | bronchial asthma / mouse asthma model / γδ T cell / TNF-α / TNF-α receptor / Vγ4T cell / MHC classI / airway remodeling |
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| Research Abstract |
Mice exposed to aerosolized ovalbumin(OVA) develop increased airway hyperresponsiveness(AHR) when deficient in γδ T cells. This finding suggests that γδ T cells function as negative regulators. The regulatory influence of γδ T cells is evident after OVA-sensitization and -challenge, and after OVA-challenge alone, but not in untreated mice. With aerosolized Abs to target pulmonary T cells, we now demonstrate that negative regulation of airway responsiveness is mediated by a small subpopulation of pulmonary γδ T cells.
TNF-α is a potent cytokine with immunomodulatory, proinflammatory and pathobiological activities. Although TNF-α is thought to play a role in mediating airway hyperresponsiveness in asthma, its function is not defined. Depletion of γδ T cells in the TNF-α transgenic mice increased AHR, whereas this depletion had no significant effect in TNF-α deficient mice. These data indicate that TNF-α can negatively modulate airway responsiveness, controlling airway function in allergen-induced AHR through the activation of γδ T cells.
The biological activities of TNF-α are mediated by two structurally related but functionally distinct receptors, p55 (TNFR1) and p75 (TNFR2), which are independently expressed on the cell surface. Depletion of γδ T cells resulted in significant increases in AHR in the p55-deficient mice, whereas no significant effect of γδ T cells depletion was evident in the p75-deficient mice. These data indicate that, in the absence of p55, where TNF-α uses the p75 pathway exclusively, the development of AHR is regulated by γδ T cells.
γδ T cells express Vγ4 and depend in their function on the presence of IFN-γ and MHC class I. Moreover, their effect can be demonstrated in the absence of αβ T cells. This novel type of negative regulation seems to precede the development of the adaptive, antigen-specific allergic response.
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Research Products
(12 results)
