Induction of human cytotoxic T cells by peptide-pulsed universal antigen presenting cells

肽脉冲通用抗原呈递细胞诱导人细胞毒性 T 细胞

基本信息

批准号：
16390294
负责人：
TSUCHIYA Shigeru
金额：
$ 9.22万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

We examined the presence of EB virus (EBV) specific cytotoxic T cells, induction of EBV specific CTLs and the cytotoxic activities of induced CTLs in the peripheral CD8+ cells from the patient with chronic active EBV infection (CAEBV) and the results were as follows,1.Demonstration of EBV specific CTLs by HLAA24-specific and EBV-specific tetramer analysisBRLF1 peptides specific CTLs were found in the peripheral lymphocytes of healthy volunteers and those of patients with infectious mononucleosis. Interestingly, we were also able to demonstrate BRLF1 peptides specific CTLs in the peripheral blood of the patients with CAEBV.2.Induction of antigen specific CTLs :We used HLAA24 positive autologous B lymphobastoid cells (B-LCLs) as antigen presenting cells and peripheral mononuclear cells were stimulated with B-LCLs, pulsed with or without BRLF1 peptide. We were successfully able to induce BRLF1 tetramer positive CTLs even in the absence of BRLF1 specific peptides. This suggested that enoug … More h BRLF1 specific stimulation were given from the EBV infected B-LCLs to specific CTLs without further peptide pulse. These CD8 positive BRLF1 tetramer specific induction and proliferation of CTLs were observed in the mononuclear cells from both healthy volunteers and the CAEBV patient.3.Cytotoxic activity of induced CTLs using interferon gamma producing ability of CTLs :Then we examined the cytotoxic activities of induced CTLs. First we confirmed that BRLF1 tetramer specific CD8+ CTLs from healthy volunteers could produce interferon gamma only after BRLF1 specific peptides. We found that the mononuclear cells from a CAEBV patient also produce BRLF1 tetramer specific CTLs after stimulation with specific peptides. However, BRLF1 specific CTLs from the patient produced interferon gamma only approximately 30%, as compared with those from the healthy volunteers approximately 50%.These results indicated the possibility that mononuclear cells from both healthy volunteers and the CAEBV patients are able to induce and proliferate specific CTLs, but cytotoxic activities of specific CTLs from the patient is reduced as compared with those of healthy volunteers. To elucidate the mechanism of the reduced CTL-activity of the CAEBV patient will have great implications to understand the etiology of CAEBV and the CTL therapy. Less

我们检查了EB病毒（EBV）特异性细胞毒性T细胞的存在，EBV特异性CTL的诱导以及来自慢性活性EBV感染（CAEBV）患者的外周CD8+细胞中诱导的CTL的细胞毒性活性，结果如下。在健康志愿者的外周淋巴细胞和感染性单核细胞增多症患者的外周淋巴细胞中发现了分析BRLF1 Pepperides的特定CTL。有趣的是，我们还能够证明患有CAEBV的患者的外周血中的BRLF1胡椒。诱导抗原特异性CTL：我们使用HLAAA24阳性自体B淋巴样细胞（B-LCLS）作为抗原呈现细胞和brl核细胞与BRLS刺激的抗原细胞（B-LCL）刺激了Blfs或Blfs persepts persepts perepts perepts perepts perepts perepts perepts perepts perepts perepts perepts perepts perepts perepts。即使没有BRLF1特异性肽，我们也能够成功地诱导BRLF1四聚体阳性CTL。这表明从EBV感染的B-LCLS向特定的CTL提供了Sough Brlf1特异性刺激，而无需进一步的肽脉冲。在健康志愿者和CAEBV患者的单核细胞中观察到了这些CD8阳性BRLF1四聚体特异性诱导和CTL的增殖。3。使用CTL的干扰素GAMMA生产能力的CTL的胞毒活性。首先，我们证实，来自健康志愿者的BRLF1四聚体特异性CD8+ CTL只能在BRLF1特异性胡椒中产生干扰素伽玛。我们发现，来自CAEBV患者的单核细胞在用特定的辣椒刺激后还会产生BRLF1四聚体特异性CTL。然而，与健康志愿者的约50％相比，患者的BRLF1特异性CTL仅产生了约30％的干扰素γ，这些结果表明，这些结果表明，健康志愿者和CAEBV患者的单核细胞都可以诱导并诱导特定的CTLS毒素，而这些患者与这些患者相比诱导了这些患者的疾病。为了阐明CAEBV患者的CTL活性降低的机制将对了解CAEBV和CTL治疗的病因具有很大的影响。较少的

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Phage ΦC31 integrase-mediated genomic integration of the common cytokine receptor gamma chain n human T-cells.

噬菌体 ΦC31 整合酶介导人类 T 细胞中常见细胞因子受体 γ 链的基因组整合。

DOI：
发表时间：
2006
期刊：
J Gene Med (In Press)
影响因子：
0
作者：
Ishikawa Y;Tanaka N;Murakami K;Uchiyama T;Kumaki S;Tsuchiya S;Kugoh H;Oshima M;Calos MP;Sugamura K
通讯作者：
Sugamura K

Lentiviral vector-mediated gene transfer in T cells from Wiskott-Aldrich syndrome patients leads to functional correction

DOI：
10.1016/j.ymthe.2004.08.008
发表时间：
2004-11-01
期刊：
MOLECULAR THERAPY
影响因子：
12.4
作者：
Dupré, L;Trifari, S;Roncarolo, MG
通讯作者：
Roncarolo, MG

Phage ψC31 integrase-mediated genomic integration of the common cytokine receptor gamma chain n human T-cells.

噬菌体 ψC31 整合酶介导人类 T 细胞中常见细胞因子受体 γ 链的基因组整合。

DOI：
发表时间：
2006
期刊：
J Gene Med 8
影响因子：
0
作者：
Ishikawa Y;Tanaka N;Murakami K;Uchiyama T;Kumaki S;Tsuchiya 5;Kugoh H;Oshima M;Calos MP;Sugamura K.
通讯作者：
Sugamura K.