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

Research of synapse formation between nervous system and regulatory T cells in melanoma lesions

黑色素瘤病灶中神经系统与调节性T细胞突触形成的研究

基本信息

批准号：
17591166
负责人：
SEO Naohiro
金额：
$ 2.24万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591166/
关键词：
Regulatory T cell Melanoma Synapse Nervous system Immune system Tumor immunity γδT cell Immune suppression γδT細胞 CD4+CD25+T細胞単クローン抗体

项目摘要

We examined whether Tregcellsandextrathymicγδ T cells, both of which have been reported to play as an immune suppressor in the formation of tumors, crosstalk with nervous system. In addition to the known molecules of Treg and γδ T cells, we identified three cell surface markers termed as R1, R68 and Y5. Sections of melanoma and melanoma-related lymph nodes were stained with polyclonal Abs and mAbs specific for R1, R68 and Y5 in combination with neuron-related Ab (GFAP, bIII tubulin) to investigate interaction of immune suppressive system with nervous system.R1, R68 and Y5 were identified by subtraction method of cDNAs from CD4+CD25+ T cells (murine and human) and γδT cells (murine). The DNA sequences with high antigenicity of R1, R68 and Y5 proteins were amplified and inserted into pDisplay vector, and then transfected with BALB3T3 or COS cell line (transformats for human genes: 3T3hR1, 3T3hR68 and 3T3hY5; transformats for murine genes: COSmR1, COSmR68, COSmY5). Polyclonal Abs were obtained by immunization BALB/c mice with 3T3hR1, 3T3hR68 and 3T3hY5, and rats with COSmR1, COSmR68 and COSmY5. Splenocytes of mice or rat immunized with each transformat were subjected to mAb preparation by fusing myeloma (P3-X63).Spleen, melanoma lesions and melanoma-related lymph nodes were separated from B6 mice obtained at 1, 2, 3 and 4 weeks after B16 inoculation. Frozen sections of spleen, melanoma lesions and melanoma-related lymph nodes, and human melanoma lesions were dual stained with polyclonal Abs or mAbs specific for R1, R68 or Y5 and neuron-related Ab specific for GFAP or βIII tubulin. While low numbers of suppressor cells interacting with nervous cells were detected at the sites of fibrous capsules of spleens and cortexes of lymph nodes, no synaptic interaction was shown in examination of melanoma lesions. Further studies using allergy or autoimmune models were necessary to demonstrate the synaptic interaction of immune suppressor cells with nervous system.

我们检查了T细胞和胸腺γδT细胞，这两种细胞都被报道在肿瘤的形成中发挥免疫抑制作用，是否与神经系统串扰。除了已知的Treg和γδT细胞分子外，我们还鉴定了三个细胞表面标记，分别为R1、R68和Y5。用抗黑色素瘤和黑色素瘤相关淋巴结的多克隆抗体和针对R1、R68和Y5的单抗与神经元相关抗体(GFAP、BIII微管蛋白)联合染色，观察免疫抑制系统与神经系统的相互作用。扩增出具有较高抗原性的R1、R68和Y5蛋白的DNA序列，将其插入pDisplay载体，分别与BALB3T3或COS细胞系(人基因3T3hR1、3T3hR68和3T3hY5；小鼠基因COSmR1、COSmR68、COSmY5)共转化。用3T3hR1、3T3hR68和3T3hY5免疫BALB/c小鼠，用COSmR1、COSmR68和COSmY5免疫大鼠，获得多克隆抗体。分别免疫小鼠和大鼠的脾细胞，制备融合骨髓瘤(P3-X63)的单抗，分别于接种后1、2、3、4周分离B6小鼠的胸腺、黑色素瘤皮损和黑色素瘤相关淋巴结。取脾、黑色素瘤病变、黑色素瘤相关淋巴结和人黑色素瘤病变冰冻切片，分别用针对R1、R68或Y5的多克隆抗体或单抗以及针对胶质纤维酸性蛋白或βⅢ微管蛋白的神经元相关抗体进行双重染色。在脾纤维包膜和淋巴结皮质处可见少量抑制细胞与神经细胞相互作用，而在黑色素瘤病变中未见突触相互作用。进一步的研究需要使用过敏或自身免疫模型来证明免疫抑制细胞与神经系统的突触相互作用。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Male New Zealand Black/KN mice : a novel model for autoimmune-induced permanent alopecia

雄性新西兰 Black/KN 小鼠：自身免疫性永久性脱发的新型模型

DOI：
发表时间：
2006
期刊：
British Journal of Dermatology 155
影响因子：
0
作者：
Akihisa Hiroi;Taisuke Ito;Naohiro Seo;Koji Uede;Takashi Yoshimasu;Ito M;Nakamura K;Natsue Ito;Ralf Paus;Fukumi Furukawa
通讯作者：
Fukumi Furukawa

Compartmental imbalance and aberrant immune function of blood CD123+ (plasmacytoid) and CD11c+ (myeloid) dendritic cells in atopic dermatitis

DOI：
10.4049/jimmunol.174.4.2396
发表时间：
2005-02-15
期刊：
JOURNAL OF IMMUNOLOGY
影响因子：
4.4
作者：
Hashizume, H;Horibe, T;Takigawa, M
通讯作者：
Takigawa, M

Future issues of percutaneous peptide immunization against tumor from the standpoint of effective activation of tumoricidal cytotoxic T lymphocytes and epidermal Langerhans cells

从有效激活杀伤细胞毒性T淋巴细胞和表皮朗格汉斯细胞的角度探讨经皮肽免疫抗肿瘤的未来问题

DOI：
发表时间：
2008
期刊：
Current Topics of Peptide & Protein Research 3
影响因子：
0
作者：
Taisuke Ito;Hidekazu Fukamizu;Natsuho Ito;Naohiro Seo;Hiroaki Yagi;Masahiro Takigawa;Hideo Hashizume;Naohiro Seo
通讯作者：
Naohiro Seo

Induction of therapeutically relevant cytotoxic T lymphocytes in humans by percutaneous peptide immunization