Project/Area Number |
10670272
|
Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Bacteriology (including Mycology)
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Research Institution | Tokyo Women's Medical University School of Medicine |
Principal Investigator |
IMANISHI Ken'ichi Tokyo Women's Medical University, Microbiology and Immunology, Associate Professor, 医学部, 助教授 (20132920)
|
Co-Investigator(Kenkyū-buntansha) |
FUJIMAKI Wakae Tokyo Women's Medical University, Instructor, 医学部, 助手 (90256496)
YAGI Junji Tokyo Women's Medical University, Assistant Professor, 医学部, 講師 (70182300)
UCHIYAMA Takehiko Tokyo Women's Medical University, Professor, 医学部, 教授 (00050550)
MIYOSHI-AKIYAMA Tohru Tokyo Women's Medical University, Instructor, 医学部, 助手 (20246466)
KATO Hidehito Tokyo Women's Medical University, Instructor, 医学部, 助手 (00241084)
田中 義正 東京女子医科大学, 医学部, 助手 (90280700)
|
Project Period (FY) |
1998 – 2000
|
Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
Keywords | T cells / differentiation / maturation / activation / superantigen / 胸腺 / 臍帯血 / アナジー |
Research Abstract |
1. We examined the responses of different stages of CD4 single positive (SP) T cells to a superantigen, TSST-1. The following results were obtained. (1) Thymic CD1a^-CD4 SP T cells are functionally mature, but CD1a^+CD4 SP T cells are not. (2) Thymic CD1a^- and cord blood (CB) CD4^+ T cells are susceptible to anergy induction, while adult peripheral blood (APB) CD4^+ T cells are not. The susceptibility to it is higher in thymic T cells than in CB T cells. (3) The majority of thymic and CB T cells are CD38^+, while CD38 expression in APB T cells is varied. Both APB CD38^+ and CD38^- CD4^+ T cells are not susceptible to anergy induction. (4) APB CD38^+CD4^+ T cells are weak in a potential to produce IL-4 and IFN-γ, while CD38^- T cells have the high potential. These results suggest that post-thymic maturation is required for thymic T cells migrating to the periphery to acquire full immunologic capability to the antigenic stimulation. 2. Studies on signal transduction in thymic and APB CD4
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^+ T cells suggest that absence of an interaction between Lck and CD45 is responsible for maintaining the anergic state of thymic CD1a^- CD4^+ T cells induced by TSST-1. 3. We discovered an emerging neonatal infectious disease, neonatal toxic shock syndrome-like exanthematous disease (NTED), which is induced by TSST-1 produced by methicilllin-resistant Staphylococcus aureus (MRSA). Then, we analyzed the activation and the response of TSST-1-reactive Vβ2^+ T cells in NTED patients during the acute and recovery phases and in asymptomatic infants exposed to MRSA.In the acute phase, Vβ2^+ T cells were anergic to stimulation with TSST-1 and underwent marked expansion, but by 2 months after disease onset, their number had declined to about 10% of the control level. On the basis of Vβ2^+ T cells activation, asymptomatic neonatal MRSA carriers were divided to two types ; type 1, Vβ2^+ T cells were activated by TSST-1 ; type 2, Vβ2^+ T cells were intact. We also observed protective role of anti-TSST-1 IgG of maternal origin against the influence of TSST-1. Less
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