1994 Fiscal Year Final Research Report Summary
Study of the pathogenesis of intrinsic asthma by establishing T cell clones
| Project/Area Number |
04454250
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Respiratory organ internal medicine
|
|---|
| Research Institution | University of Tokyo |
|---|
Principal Investigator |
ITO Koji University of Tokyo, Faculty of Medicine, professor, 医学部(病), 教授 (10008310)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MORITA Yutaka Univ. of Tokyo, Faculty of Medicine, associate prof., 医学部(病), 助教授 (60107620)
TAKIZAWA Hajime Univ. of Tokyo, Faculty of Medicine, assistant prof., 医学部(病), 助手 (80171578)
MORI Akio Univ. of Tokyo, Faculty of Medicine, assistant professor, 医学部(病), 助手 (80251247)
SUKO Mastunobu Univ. of Tokyo, Faculty of Medicine, lecturer, 医学部(病), 講師 (80107622)
OKUDAIRA Hirokazu Univ. of Tokyo, Faculty of Medicine, lecturer, 医学部(病), 講師 (30106645)
|
|---|
| Project Period (FY) |
1992 – 1994
|
| Keywords | Bronchial asthma / T cell / eosinophil / Interleukin-5 / T cell clone |
|---|
| Research Abstract |
Chronic eosinophilic inflammation of bronchial mucosa has been recognized in the pathophysilology of bronchial asthma. The roles of T cells and T cell cytokines, including especially IL-5, have been strongly implicated in the local infiltration and activation of eosinophils. We have indicated that enhanced IL-5 production by CD4^+ T cells is observed in both atopic and non-atopic (intrinsic) asthmatics. Control of IL-5 production by activated T cells must be a beneficial approach to manage allergic diseases characterized by eosinophilic inflammation. In order to delineate the precise mechanisms of IL-5 production by human "allergic" T cells, we established T cell clones from asthmatic patitents and analyzed cytokine production by those helper T cell clones. Both PKC activation and Ca^<++> influx were required for IL-5 synthesis. The transcription factors, NF-AT and AP-1 were suggested to be involved in IL-5 gene transcription. IL-5 synthesis by human T cells was dependent on endogeneously produced IL-2. Human recombinant IL-2 initiated IL-5 gene transcription in IL-5 producing T cell clones. PBMC of some intrinsic asthmatics produced IL-5 in response to mite allergen extract. T cell clones established from such patients did produce IL-5 in response to mite allergen, suggesting that mite allergen might be in part responsible for so called "intrinsic" asthma.
|
