2001 Fiscal Year Final Research Report Summary
Intracellular signal transduction of activated T cells and anergic T cells
| Project/Area Number |
11670276
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Bacteriology (including Mycology)
|
|---|
| Research Institution | Tokyo Woman's Medical University |
|---|
Principal Investigator |
FUJIMAKI Wakae Tokyo Women's Medical University, School of Medicine, Lecture Instructor, 医学部, 講師 (90256496)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YAGI Junji Tokyo Women's Medical University, School of Medicine, Lecture Instructor, 医学部, 講師 (70182300)
IMANISHI Kenichi Tokyo Women's Medical University,School of Medicine, Associate Professor, 医学部, 助教授 (80124527)
UCHIYAMA Takehiko Tokyo Women's Medical University, School of Medicine, Professor, 医学部, 教授 (00050550)
|
|---|
| Project Period (FY) |
1999 – 2001
|
| Keywords | bacterial super-antigen / human T-cell / post-thymi c maturation / signal transduction / Lck / CD45 / T-cell subsets |
|---|
| Research Abstract |
Human T cells show different biological responses according to T-cell maturation or subsets when stimulated with bacterial superantigens. We addressed the question why the T cells response in different way by comparing signal transduction.
1. Human thymic CD1a^-CD4^+ T cells in the final stage of thymic maturation are susceptible to anergy induced by bacterial superantigens, whereas adult peripheral blood (APB) CD4^+ T cell are not only induced to anergic state but also exhibit high responses by restimulation. The tyrosine kinase activity of lck increased after restimulation in APB CD4^+ T-cell blasts but not in thymic CD4^+ T-cell blasts. The Lck was highly tyrosinphosphorylated in both types of T-cell blasts before restimulation. After restimulation, it was markedly dephosphorylated in APB CD4^+ T-cell blasts but not in thymic CD4^+ T-cell blasts. Confocal microscopy demonstrated that colocalization of Lck and CD45 was induced in restimulated APB CD4^+ T-cell blasts but not in thymic CD4^+ T-cell blasts. Further, remarkable accumulation of Lck in the membrane raft was observed in restimulated APB CD4^+ T-cell blasts but not in thymic CD4^+ T-cell blasts. These data indicate that interaction between Lck and CD45 is important for T- cell activation and that the interaction is suppressed physically in thymic CD4^+ T-cell blasts and plays a critical role in sustaining an anergic state.
2. Next, we examined superantigen-induced responses of APB CD4^+ and CD8^+ T-cell subsets in vitro. The proliferative response and IL-2/IL-4 production were higher in CD4^+ T-cell subset than in CD8^+ T-cell subset, while IFN-y production and cytotoxic activity on MHC class II^+ cells were higher in the CD8^+ subset than in the CD4^+ subset. These data indicate that CD4^+ and CD8^+ 1-cell subsets are activated by bacterial superantigens in specific ways. Now we try to confirm that Lck regulation is related with the different responses.
|
