2006 Fiscal Year Final Research Report Summary
Strategies to control the generation of effective T cell memory.
| Project/Area Number |
16043209
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Chiba University |
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Principal Investigator |
SAKAMOTO Akemi Chiba University, Graduate School of Medicine, Research Associate, 大学院医学研究院, 助手 (90359597)
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| Project Period (FY) |
2003 – 2006
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| Keywords | Bc16 / memory T cell / CD8 Tcell / CD4 T cell / granzyme B / Interferon-g / transcriptional factor / gene expression |
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| Research Abstract |
Molecular mechanisms involved in the generation of immune memory cells are largely unknown and their elucidation is the key to design strategies to control the generation of immunity. In this study, w e focused on the role of Bd6 in the memory T cell generation to get better understanding of the mechanisms of generation and maintenance of the memory T cell.
1. Role of Bd6 in the generation of memory CD8 T cell and its target gene
We found that Bc16 acts as an amplifier for generation and prolifererative capacity of central memory CD8 T cells. And we also confirmed that granzyme B is a target gene of Bd6 in effector CD8 T cell. As the mechanisms of this regulation, Bd6 recruits histone deacetylase at the promoter of granzyme B and competes against STAT binding using the simmerer sequence for DNA binding. Granzym B is the most important functional molecule, for dearance of virus. But recently, serine protease granzyme B is reported as a factor for inducing suicide of the CD8 T cell itself These data indicate that control of expression of granzyme B by Bc16 is one of the mechanisms for effective memory CD8 T cells.
2. Role of Bc16 in the memory CD4 T cell generation
CD4 T cell is important to generate functional memory after infection. Bc16 expression is induced in activated CD4 T cells, but the role for Bc16 in the memory CD4 T cells is not known. Then D011.10 back Bc16 deficient mouse were obtained and role of Bc16 during memory CD4 T cells was examined. Bc16 deficient CD4 T cells showed impaired generation of long-term memory CD4 T cells in vivo. From the functional analysis, IFN-y negative CD4 T cells were gradually decreased in Bc16 deficient CD4 T cells. IFN-y negative CD4 T cells include long-lived CD4 T cells. Thus Bc16 is required for the generation and maintenance of long-term memory CD4 T cells,
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