2001 Fiscal Year Final Research Report Summary
Development of the gene therapy model for allergic diseases
| Project/Area Number |
12557046
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 展開研究 |
|---|
| Research Field |
内科学一般
|
|---|
| Research Institution | Chiba University |
|---|
Principal Investigator |
TOKUHISA Takeshi Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (20134364)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OKADA Seiji Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (50282455)
HATANO Masahiko Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (20208523)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Keywords | BCL6 / Allergic inflammation / Germinal center / Memory B cells / Transgenic mice / IL-5 / Gene therapy / Eosinophil |
|---|
| Research Abstract |
BCL6-KO mice display no germinal center formation and severe allergic inflammation with eosinophilic infiltration. We found that one of the target gene of BCL6 in T cells is the IL-5 gene. In this project, we investigated the functional role of BCL6 in memory B cell development and tried to develop the gene therapy model for allergic diseases by establishing model animals in which expression of BCL6 is controlled. We show that (1) BCL6-KO mice produced control levels of secondary IgG1 antibodies, and generated transferable IgG1 memory B cells in the spleen. Mutation in the V-hedvy gene was nil in those memory B cells. We have established transgenic mice carrying the Ig-BCL6, and the germinal center formation and memory responses were augmented in transgenic mice. Therefore, Bcl6 is essential for somatic hypermutation and generation of memory B cells in germinal centers. (2) We have established transgenic mice carrying the lck-BCL6 gene. When splenic T cells from lck-BCL6 mice were stimulated with anti-CD3 antibody, IL-5 production was specifically suppressed. Those lck-BCL6 mice were mated with BCL6-KO mice and the allergic inflammation in BCL6-KO mice was completely controlled. We have established the gene transfer method using virus vectors. We wish to develop the efficient gene therapy method for allergic diseases near future.
|
