Project/Area Number |
18590439
|
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 Women's Medical University |
Principal Investigator |
IMANISHI Kenichi Tokyo Women's Medical University, School of Medicine, Associate Professor (20132920)
|
Co-Investigator(Kenkyū-buntansha) |
KATO Hidehito Tokyo Women's Medical University, School of Medicine, Assistant Professor (00241084)
内山 竹彦 東京女子医科大学, 医学部, 教授 (00050550)
|
Project Period (FY) |
2006 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
Keywords | infectious diseases / T cells / superantigen / co-stimulation / 感染症 |
Research Abstract |
1. Most newborn patients with neonatal toxic shock syndrome (TSS)-like exanthematous disease (NTED),exhibit mild clinical symptoms. We present the case of a patient with NTED who exhibited exceptionally severe clinical symptoms and an adult-type T cell response to the causative toxin TSS toxin-1. The view that TSST-1induced T cell activation is primarily involved in the generation of pathologic changes in TSS and NTED would explain clearly that the adult type high T cell response is mainly responsible for the generation of severe clinical symptoms in our neonatal patient. 2. We identified seven novel variants of streptococcal pyrogenic exotoxin G (SPEGG), a superantigen, in Streptococcus dysgalactiae subsp. dysgalactiae or equisimilis isolates from clinical cases of infection in humans and animals. SPEGGs selectively stimulated bovine T cells bearing V131, 10 and V134. Bovine serum showed reactivity to the rSPEGG proteins. These results indicated that SPEGGs have properties as superanti
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gens, and it is likely that SPEGGs play a pathogenic role in animals. 3. Streptococcus dysgalactiae-derived mitogen (SDM) is a novel superantigen that is distinct from other known superantigens based on phylogenetic analysis. The X-ray structure of SDM has been determined at 1.95 A resolution. SDM shares the same characteristic fold with other superantigens, but it shows a major structural difference due to the lack of the a5 helix between the 1310 and 011 strands. A bound zinc ion was identified in the structure at the C-terminal domain of the molecule. SDM appears to bind to the major histocompatibility complex class II I3-chain through the zinc-binding site. 4. Chronic focal infections are closely related to pustulosis palmaris et plantaris (PPP). In patients that had undergone a tonsillectomy or dental treatment, the clinical activities of PPP, the expressions of ICOS and various other activation markers on T cells were examined. The above treatments for focal infections led to a dramatic and persistent improvement in the PPP skin lesions and pustulotic arthro-osteitis. The expression of ICOS, but not of other activation markers, was higher in tonsil tissues from PPP patients than in tonsil tissues from non-PPP patients. The activation of T cells via ICOS co-stimulation in focal infections likely triggers the skin and skeletal inflammation associated with PPP, resulting in tissue damage. Less
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