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The roles of deltagamma T cells in host defense mechanism

δT细胞在宿主防御机制中的作用

基本信息

批准号：
06044102
负责人：
YOSIKAI Yasunobu
金额：
$ 2.5万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

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.

在细菌感染、急性移植物抗宿主病（GVHD）和妊娠期间出现的γ δ T细胞在小鼠中被表征。在沙门氏菌感染期间出现的γ δ T细胞表达V δ 5、6或7，并响应于热灭活的沙门氏菌或自体脾细胞而增殖。这些γ δ T细胞的表型为IL-2 R α ^-β ^+ γ ^+，不产生IL-2，而γ δ T细胞表达大量的IL-15 mRNA，并在重组IL-15的作用下显著增殖。沙门氏菌病时出现的γ δ T细胞可能以IL-15代替IL-2作为生长因子，γ δ T细胞经TCR刺激后易发生凋亡，γ δ T细胞经TCR刺激后胞内Ca^++维持不变，而α T细胞经TCR刺激后胞内Ca^++迅速下调。肠上皮内淋巴细胞（IEL）中γ δ T细胞对组成性表达Fas受体的内分泌细胞具有杀伤活性，Fas Ig融合蛋白可显著抑制IEL中γ δ T细胞的杀伤活性。在急性GVHD期间，IEL表达大量的Fas-L，并显示出对Fas^+细胞的细胞毒活性增加。I-IEL中的γ δ T细胞可能通过Fas-Fas-L系统参与了急性移植物抗反应（GVHD）肠病的发病过程，妊娠期子宫γ δ T细胞处于激活状态，并通过TGF-β的产生抑制抗胎儿MHC反应。子宫γ δ T细胞可能通过产生TGF β在母体抗胎儿反应的免疫调节中发挥重要作用。