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Development of dendritic cells and functional regulation of host T cell responses in mice with concurrent multiple parasitic infections

并发多种寄生虫感染的小鼠中树突状细胞的发育和宿主 T 细胞反应的功能调节

基本信息

批准号：
15390137
负责人：
OHTA Nobuo
金额：
$ 9.73万
依托单位：
Tokyo Medical and Dental University (2005)Nagoya City University (2003-2004)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

Immunological mechanisms of Th1/Th2 dichotomy during multiple parasitic infection were investigated. A/J mice were susceptible to Plasmodium chabaudi (Pc) infection, however, mice concurrently infected with Schistosoma mansoni (Sm) became resistant to the malaria possibly through enhanced IFNγ production. The hypothesis was functional alterations in dendritic cells (DC)-T cells interaction during-the concomitant infected mice. DC, both splenic and myeloid, of A/J mice were not activated under the stimulation of soluble egg antigen of S.mansoni in vitro. When surface phenotypes of DC were compared between mice co-infected or malaria alone, frequency of CD8^+ DC were lower in the co-infected A/J mice than susceptible control A/J mice. This suggested that CD8^+ dendritic cells might be involved in resistant mechanism of A/J mice against Pc infection. Although upregulated IFNγ production was observed in co-infected mice, DC did not show enhanced IL-12 production. Direct effects of DC were tested by cell transfer experiments from co-infected mice to naive mice. So far at the cell number we tested, there was no evidence that DC can transfer the resistance of A/J mice against Pc. On the other hand, functional diversities of T cells could affect the susceptibility of A/J mice to Pc. Induction of Treg cells was compared among different infectious situation of A/J mice. Apparent difference was observed for the frequency of Treg cells. In the co-infected mice, which were resistant to Pc, showed higher frequency of Treg cells compared with control Pc infection. More over, co-infected mice treated with anti-CD25 mAb became susceptible to Pc again. Together, it was suggested that resistance to P.chabaudi during co-infection of S.mansoni seemed to be regulated by Treg cells, while involvement of dendritic cells was not clearly shown

探讨了多种寄生虫感染时Th 1/Th 2二分的免疫学机制。A/J小鼠对夏氏疟原虫（Pc）感染敏感，而同时感染曼氏血吸虫（Sm）的小鼠可能通过增强IFNγ的产生而产生抗疟作用。这一假说是在同时感染小鼠的过程中树突状细胞（DC）-T细胞相互作用的功能改变。曼氏血吸虫虫卵可溶性抗原在体外刺激A/J小鼠的脾和髓系DC时，DC均未被激活。当比较共感染小鼠和单独感染疟疾小鼠的DC表面表型时，共感染A/J小鼠中CD 8 ^+ DC的频率低于易感对照A/J小鼠。提示CD 8 ^+树突状细胞可能参与了A/J小鼠对Pc感染的抵抗机制。虽然在共感染小鼠中观察到IFNγ产生上调，但DC未显示IL-12产生增强。DC的直接作用通过从共感染小鼠到幼稚小鼠的细胞转移实验来测试。到目前为止，在我们测试的细胞数，没有证据表明DC可以转移A/J小鼠对Pc的抵抗。另一方面，T细胞功能的失调可能影响A/J小鼠对Pc的易感性。比较不同感染状态下A/J小鼠Treg细胞的诱导情况。Treg细胞的频率观察到明显差异。与对照组相比，联合感染组小鼠Treg细胞的表达率明显增高，而联合感染组小鼠对Pc具有抵抗力。更重要的是，用抗CD 25 mAb治疗的共感染小鼠再次变得对Pc易感。总之，这表明在曼氏血吸虫共感染期间对夏氏疟原虫的抗性似乎受到Treg细胞的调节，而树突状细胞的参与没有明确显示

项目成果

期刊论文数量（21）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Roles of FcεRIIB in nasal eoshinophilia and IgE production in murine allergic rhinitis.

FcεRIIB 在小鼠过敏性鼻炎鼻嗜酸性粒细胞增多和 IgE 产生中的作用。

DOI：
发表时间：
2004
期刊：
Am J Resir Crit Care Med 169
影响因子：
0
作者：
Watanabe T;Okano M;Hattori H;Yoshino T;Ohno N;Ohta N;Sugata Y;Osada Y;Takai T;Nishizaki K.
通讯作者：
Nishizaki K.

Roles of FcεRIIB in nasal eosinophilia and IgE production in murine allergic rhinitis.

FcεRIIB 在小鼠过敏性鼻炎鼻腔嗜酸性粒细胞增多和 IgE 产生中的作用。

DOI：
发表时间：
2004
期刊：
Am J Resir Crit Care Med 169
影响因子：
0
作者：
Watanabe T;Okano M;Hattori H;Yoshino T;Ohno N;Ohta N;Sugata Y;Orita Y;Takai T;Nishizaki K.
通讯作者：
Nishizaki K.

Kumagai T 他: "Effects of CpG oligonucleotides on Schistosoma Japonicum infection in mice"Nagoya Med J. 46(2). 99-110 (2003)

Kumagai T等人：“CpG寡核苷酸对小鼠日本血吸虫感染的影响”Nagoya Med J.46(2)(2003)。