2007 Fiscal Year Final Research Report Summary
Molecular mechanisms of inhibition of T cell functions by mycobacterial infection-induced suppressor macrophages
| Project/Area Number |
18590422
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Shimane University |
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Principal Investigator |
SHIMIZU Toshiaki Shimane University, Facolty of medicine, Assistant Professor (60284030)
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| Co-Investigator(Kenkyū-buntansha) |
TOMIOKA Haruaki Shimane University, Faculty of medicine, Professor (40034045)
TATANO Yutaka Shimane University, Faculty of medicine, Assistant Professor (70432614)
YASUMOTO Kou Shimane University, Faculty of medicine, Assistant Professor (00448200)
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| Project Period (FY) |
2006 – 2007
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| Keywords | mycobacterial infection / Mycobacterium avium complex / suppressor macrophage / T cell / cell-to-cell contact / signal transduction / tyrosine phosphorylation / aldose reductase |
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| Research Abstract |
We previously found that suppressor macrophages (S-Mφs) induced by Mycobacterium avium complex infection affect tyrosine (Tyr) dephosphorylation of several cytoplasmic proteins including aldose reductase (AR) of target T cells with the expression of immunosuppressive activity of S-Mφs. In this study, we examined the profiles of S-Mφ-mediated dephosphorylation of AR in the target T cells and following findings were obtained. (1) Anti-phosphotyrosine antibody bound to AR protein in mouse T cell lysates and recombinant human AR protein (rAR) derived from baculovirus expression system. (2) Since Tyr-40 is located at consensus sequences ([R,K]-x(3)-[D,E]-x(2)-Y) for tyrosine kinase phosphorylation site, Tyr-40 is a candidate for phosphorylation site in mouse AR protein. (3) Anti-phosphoserine antibody also bound to rAR. (4) AR protein was constitutively expressed in resting T cells. In separate experiments, co-cultivation of target T cells with S-Mφs did not cause marked changes in profiles of the expression levels of AR protein in target T cells. (5) Anti-CD3/anti-CD28 monoclonal antibody (mAb)-induced T cell mitogenesis were strongly suppressed by AR inhibitor. In addition, when target T cells were co-cultivated with S-Mφs, anti-CD3/anti-CD28 mAb-induced activation of MAP kinases (Erk-1,-2) in target T cells were not blocked. These findings suggest that AR is not essential for TCR/Ras/Erk signaling pathway in anti-CD3/anti-CD28 mAb-stimulated T cells, whileas AR may be involved in CD28/Akt/NF〓B-mediated signaling pathway in target T cells. Further studies are currently underway to identify protein tyrosine phosphatases which mediate the dephosphorylation of AR in target T cells.
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Research Products
(112 results)
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[Journal Article] Antimicrobial activity of picolinic acid against extracellular and intracellular Mycobacterium avium complex and its combined activity with clarithromycin, rifampicin, and fluoroquinolones2006
Author(s)
Cai, SS., Sato, K., Shimizu, T., Yamahe, S., Hiraki, M., Sano, C., Tomioka, H
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Journal Title
Journal of Antimicrobial Chemotherapy 57 (1)
Pages: 85-93
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Effects of chitin, chitosan, and oligochitosan on the antimicrobial activity of clarithromycin in combination with rifampicin against Mycobacterium avium complex within mouse peritoneal macrophages2006
Author(s)
Sato, K., Shimizu, T., Sano, C., Yamabe, S., Tomioka, H
Organizer
The 81st annual meeting of the Japanese society for tuberculosis
Place of Presentation
Sendai
Year and Date
2006-04-28
Description
「研究成果報告書概要(欧文)」より
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