Project/Area Number |
06044102
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Research Category |
Grant-in-Aid for international Scientific Research
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Allocation Type | Single-year Grants |
Section | Joint Research |
Research Institution | Nagoya University |
Principal Investigator |
YOSIKAI Yasunobu Nagoya University, School of Medicine, 医学部, 教授 (90158402)
|
Co-Investigator(Kenkyū-buntansha) |
BLUESTONE Je シカゴ大学, ベンメイ研究所, 教授
HIROMATSU Kenji Nagoya University, School of Medicine, 医学部, 助手 (80252237)
BLUESTONE Jeffrey a. The Ben May Institute, THe University of Chicago
|
Project Period (FY) |
1994 – 1995
|
Project Status |
Completed (Fiscal Year 1995)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1994: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
Keywords | gammadelta T cells / IL-15 / Bacterial intection / Pregnant uterus / IEL / immunorgulation / γδ型T細胞 / ストレス蛋白質 / TCR遺伝子 / 自己反応性 / アポトーシス |
Research Abstract |
The gammadelta T cells appearing during bacterial infection, acute graft versus host disease (GVHD) and pregnancy were characterized in mice. gammadelta T cells appearing during infection with Salmonella expressed Vdelta5,6 or 7, and proliferated in response to heat-killed Salmonella or autologus spleen cells. These gammadelta T cells were IL-2Ralpha^-beta^+gamma^+ of phenotype and did not produce IL-2, while the gammadelta T cells express an abundant level of IL-15 mRNA and proliferate significantly in response to recombinant IL-15. The gammadelta T cells appearing during salmonellosis may use IL-15 as growth factor instead of IL-2. The gammadelta T cells are easily subjected to apoptosis after stimulation via TCR.The intracellular Ca^<++> was sustained in the gammadelta T cells after the stimulation, while the alphabeta T cells could down-modulate the cytosolic Ca^<++> rapidly after the stimulation. The sustained cytosolic Ca^<++> may be related to apoptosis of gammadelta T cells. The gammadelta T cells in intestinal intraepithelial lymphocytes i-(IEL) exhibited a cytotoxic activity against entrocytes which constitutively expressed Fas receptor and the cytotoxicity was significantly inhibited by Fas-Ig fusion protein. During acute GVHD,the IEL expressed abundant levels of Fas-L and showed increased cytotoxic activity against Fas^+ cells. The gammadelta T cells in I-IEL may contribute to the pathogenesis of enteropathy during acute graft versus reaction (GVHD) via Fas-Fas-L system. Uterine gammadelta T cells in activated stae were increased during pregnancy nad suppressed the anti-fetal MHC response via TGF-b production. The uterine gammadelta T cells may play important roles in immunoregulation of maternal anti-fetal responses via production of TGFbeta.
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