权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Functional analysis of peripheral tolerance

外周耐受功能分析

基本信息

批准号：
08457108
负责人：
KOYASU Shigeo
金额：
$ 4.93万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457108/
关键词：
self-tolerance lpr transgenic mouse T cell receptor MAP kinase superfamily 1pr インターロイキン2 CD28

项目摘要

1)Signals generated by TCR slimulation alone is not sufficient to activate IL2 gene and thus induces anergy in resting T cells. We found that TCR stimulation alone induces activation of MAPK/ERK but not SAPK/JNK and p38/CSBP.When T cells were stimulated through both TCR and CD28, all three MAPK superfamily members were activated.2)SAPK/JNK and p38/CSBP pathways form redundant pathways and MAPK/ERK pathway syuergistically functions with SAPK/JNK and p38/CSBP pathways in activation of IL2 gene.3)Activation of SAPK/JNK and p38/CSBP pathways but not MAPK/ERK pathway are sensitive to cyclosporin A.Activation of SAPK/JNK and p38/CSBP pathways by osmotic shock is not inhibited by cyclosporin A, suggesting the existence of a cyclosporin A sensitive step between TCR/CD28 and activation of SAPK/JNK and p38/CSBP pathways.4)When peripheral T cells from HY/rag-2^% mice specific for a male antigen HY in the presence of H-2D^b were injected into male B6-Ly5.2-rag-2^% mice, donor derived cells were activated and increased in the recipient body. But after a while the cell numbers decreased to an undetectable level. In contrast, when peripheral T cells from HY/lpr/rag-2^% mice were used, such decrease in cell numbers was not observed because of the lack of Fas/FasL induced cell death. Instead, cell numbers increased and eventually reached a plateau level. Such cells do not respond to antigen in vitro but they restore the reactivity against antigen after transfer into female mice.We are planning to isolate such "in vivo induced anergic cells" and analyze their characteristics such as surface phenotype and signal transduction machinery downstream of the TCR.

1)单独由TCR SLIMULATION产生的信号不足以激活IL 2基因，从而诱导静息T细胞无反应性。我们发现，单独刺激TCR可诱导MAPK/ERK的激活，但不诱导SAPK/JNK和p38/CSBP的激活。2）SAPK/JNK和p38/CSBP通路形成冗余通路，MAPK/ERK通路与SAPK/JNK和p38/CSBP通路在IL-2基因的激活中协同作用; 3）SAPK/JNK和p38/CSBP通路的激活与MAPK/ERK通路的激活有关。CSBP通路而不是MAPK/ERK通路对环孢菌素A敏感。由渗透压休克引起的SAPK/JNK和p38/CSBP通路的激活不被环孢菌素A抑制，提示在TCR/CD 28与SAPK/JNK和p38/CSBP通路的活化之间存在环孢菌素A敏感步骤。4）当来自HY/rag-2 μ %小鼠的外周T细胞在H-28存在下对雄性抗原HY特异时，将2D-b注射到雄性B6-Ly5.2-rag-2^%小鼠中，供体来源的细胞在受体体内被激活并增加。但过了一段时间，细胞数量下降到无法检测的水平。相反，当使用来自HY/lpr/rag-2 μ %小鼠的外周T细胞时，由于缺乏Fas/FasL诱导的细胞死亡，没有观察到细胞数量的这种减少。相反，细胞数量增加并最终达到平台水平。这种细胞在体外对抗原没有反应，但在转移到雌性小鼠体内后，它们对抗原的反应性恢复。我们计划分离这种“体内诱导的无反应性细胞”，并分析它们的特性，如表面表型和TCR下游的信号传导机制。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Nishizawa, K., and Koyasu, S.: "IL2 and IL7 differentially induce CD4^-CD8^-αβTCR^+NK1.1^+ large granular lymphocytes and IL4 producing cells from CD4^-CD8^-αβTCR^+NK1.1^- cells:implications for the regulation of Th1 and Th2 type responses." Int.Immunol.9

Nishizawa, K. 和 Koyasu, S.：“IL2 和 IL7 差异性地诱导 CD4^-CD8^-αβTCR^+NK1.1^+ 大颗粒淋巴细胞和来自 CD4^-CD8^-αβTCR^+NK1 的产生 IL4 的细胞。 1^- 细胞：Th1 和 Th2 型反应调节的影响。” Int.Immunol.9