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GAMMA/DELTA T CELLS IN TOLERANCE AND TUMOR IMMUNITY

GAMMA/DELTA T CELLS IN TOLERANCE AND TUMOR IMMUNITY
GAMMA/Delta T 细胞在耐受性和肿瘤免疫方面的作用
批准号:
6376248
负责人:
JUDITH A KAPP
金额:
$24.17万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1996
资助国家:
美国
项目状态:
已结题
起止时间:
1996-05-01 至 2003-04-30

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项目成果

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中文摘要
翻译
描述(改编自研究者摘要):本更新申请的长期目标是确定γ/δ T细胞和非细胞溶解性α/β T细胞如何调节对作为外源性抗原、内源性抗原和肿瘤抗原的OVA的耐受性。将使用在CD 8 + T细胞(TCR-1)或CD 4 + T细胞(OT-11)上表达OVA特异性TCR的转基因小鼠和各种敲除小鼠来探索控制耐受性发展的生理信号。第一个目的是表征来自表达转基因TCR-1 T细胞和从上皮内淋巴细胞克隆的γ/δ T细胞的B6小鼠的非细胞溶解性CD 8 + T细胞。将通过过继转移到γ/δ TCR缺陷小鼠中来研究γ/δ T细胞与非细胞溶解性CD 8 + T细胞之间的相互作用。表达转基因OT-11 T细胞的受体将用于确定非细胞溶解性CD 8 + T细胞如何抑制抗体应答。在第二个目的中,将使用TCR-1小鼠评价OVA转基因小鼠中γ/δ T细胞和非细胞溶解性CD 8 + T细胞的功能。将在第三个目标中检验E.G7-OVA诱导肿瘤特异性耐受的假设。如果发现耐受性,研究者将确定CD 8 + T细胞是否缺失、无反应性或显示功能改变。将测试用共刺激分子转染的E.G7-OVA肿瘤逆转耐受性的能力。将确定诺斯卡品对肿瘤特异性耐受和免疫的细胞和分子作用。这些研究的结果应该为开发那可汀的人体临床试验提供基础。
英文摘要
DESCRIPTION (Adapted from Investigator's Abstract): The long-term goal of this renewal application is to determine how gamma/delta T cells and non-cytolytic alpha/beta T cells regulate tolerance to OVA as an exogenous antigen, an endogenous antigen and as a tumor antigen. Transgenic mice expressing OVA-specific TCR on CD8+ T cells (TCR-1) or CD4+ T cells (OT-11) and a variety of knockout mice will be used to explore the physiological signals that control development of tolerance. The first aim is to characterize non- cytolytic, CD8+ T cells from B6 mice expressing transgenic TCR-1 T cells and gamma/delta T cells cloned from intra-epithelial lymphocytes. Interactions between gamma/delta T cells and non- cytolytic, CD8+ T cells will be studied by adoptive transfer into gamma/delta TCR deficient mice. Recipients expressing transgenic, OT-11 T cells will be used to determine how non-cytolytic CD8+ T cells inhibit antibody responses. In the second aim, the function of gamma/delta T cells and non-cytolytic CD8+ T cells in OVA transgenic mice will be evaluated using TCR-1 mice. The hypothesis that E.G7-OVA induces tumor-specific tolerance will be tested in the third aim. If tolerance is found, the investigator will determine whether CD8+ T cells are deleted, anergic or display altered functions. The ability of E.G7-OVA tumors transfected with a co-stimulatory molecule to reverse tolerance will be tested. The cellular and molecular effects of noscapine on tumor-specific- tolerance and immunity will be identified. Results from these studies should provide the basis for developing clinical trials of noscapine in humans.
期刊论文(7)
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会议论文
DOI: 10.4049/jimmunol.158.8.3610
发表时间: 1997-04
期刊: Journal of immunology
影响因子: 4.4
作者: [Yong Ke;K. Pearce;J. Lake;H. Ziegler;J. Kapp]
通讯作者: Yong Ke;K. Pearce;J. Lake;H. Ziegler;J. Kapp
DOI: 10.1084/jem.187.1.49
发表时间: 1998-01-05
期刊: The Journal of experimental medicine
影响因子: --
作者: [Ke Y, Ma H, Kapp JA]
通讯作者: Kapp JA
Antigenic epitopes regulate the phenotype of CD8+ CTL primed by exogenous antigens.
抗原表位调节由外源抗原引发的 CD8 CTL 的表型。
DOI: 10.4049/jimmunol.164.11.5698
发表时间: 2000
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者: [Ma,H, Kapp,JA]
通讯作者: Kapp,JA
Retinal Cell Transplantation Tolerance and Rejection
Retinal Cell Transplantation Tolerance and Rejection
Retinal Cell Transplantation Tolerance and Rejection
Retinal Cell Transplantation Tolerance and Rejection
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