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GAMMA/DELTA T-CELL FUNCTION IN INTESTINE & SKIN IMMUNITY

肠道中的 GAMMA/Delta T 细胞功能

基本信息

批准号：
2607810
负责人：
WAYNE T. MCCORMACK
金额：
$ 10.96万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-12-01 至 1999-11-30
项目状态：
已结题

项目摘要

Human gamma delta T cells are involved in chronic inflammation and in immune response to intracellular infections. The specific localization of human gamma delta T cells in disease lesions of the intestinal epithelium and skin suggest important functional roles in immune surveillance of these sites, possibly via recognition of microbial antigens and/or damage-induced self antigens. Interestingly, the intestine is also now recognized as a site of extrathymic T cell differentiation in the mouse. The prevalence of gamma delta T cells in the chicken immune system suggests a selective advantage and a greater functional role of gamma delta T cell development and function. In this revised grant application, the chicken is presented as an animal model in which to study gamma delta T cells of extrathymic origin and their functional role in response to pathogens invading the intestinal epithelium and inflammation of the skin. First, the exquisite specificity of thymic gamma delta T cell suppression in chickens by embryonic mAb treatment, without effects on alphabeta T cells or B cells, will be used to test the hypothesis that the gamma delta T cell first line of defense develops in epithelial tissues. Extrathymic sites of gamma delta T cells will be compared. Extrathymic sites, including the intestinal epithelium, will be probed with mAb to chicken thymic stromal elements to identify shared features of thymic and extrathymic microenvironments that support gamma delta T cell development. The natural occurrence of environmental pathogens that invade the chicken intestinal epithelium (Eimeria and Salmonella) will be used to test the hypothesis that gamma delta T cells of extrathymic origin are the functionally relevant population responding to epithelial infections. Comparison of the expressed gamma delta TCR repertoires of gamma delta T cells in normal and infected chickens will provide insights as to the nature of the antigen recognized by gamma delta T cells (e.g. microbial antigens or superantigens vs. damage-induced epithelial cell antigens or superantigens). A chicken line characterized by inherited scleroderma involving gamma delta T cell infiltration will be used to examine the functional role of gamma delta T cells in skin inflammation by determining the effect of thymic gamma delta T cells suppression on disease progression, and to test the trauma signal hypothesis in the absence of a resident skin gamma delta T cell population with a homogeneous TCR. This animal model will provide significant insights into the evolution of the gamma delta TCR and the function of gamma delta T cells under pathological conditions of the intestinal epithelium and skin.

人类γ δ T细胞参与慢性炎症和免疫反应。对细胞内感染的免疫反应。具体定位人γ δ T细胞在肠道疾病病变中的作用上皮和皮肤在免疫中具有重要功能作用监测这些地点，可能通过识别微生物抗原和/或损伤诱导的自身抗原。有趣的是肠现在也被认为是胸腺外T细胞小鼠的分化。 γ δ T细胞的患病率鸡的免疫系统显示出选择性优势， γ δ T细胞发育和功能的功能作用。在这修改拨款申请，鸡作为动物模型研究胸腺外来源的γ δ T细胞及其对侵入肠道的病原体的反应中的功能作用上皮和皮肤炎症。一、精致鸡胸腺γ δ T细胞抑制特异性胚胎mAb处理，对α T细胞或B细胞没有影响，将被用来检验γ δ T细胞首先在上皮组织中形成了一条防线。胸腺外部位将比较γ δ T细胞。胸腺外部位，包括肠上皮，将用鸡胸腺基质的mAb探测确定胸腺和胸腺外的共同特征的要素支持γ δ T细胞发育的微环境。的自然发生的环境病原体侵入鸡肠上皮（艾美耳球虫和沙门氏菌）将用于检测假设胸腺外来源的γ δ T细胞是功能相关人群对上皮感染的反应。 γ δ TCR表达谱的比较正常和受感染鸡的T细胞将提供关于由γ δ T细胞识别的抗原的性质（例如微生物抗原或超抗原与损伤诱导的上皮细胞抗原或超抗原）。以遗传性硬皮病为特征的鸡品系涉及γ δ T细胞浸润将用于检查 γ δ T细胞在皮肤炎症中的功能作用测定胸腺γ δ T细胞抑制对疾病进展，并测试创伤信号假说，不存在具有以下特征的常驻皮肤γ δ T细胞群体：同源TCR。这种动物模型将提供重要的见解 γ δ TCR的进化和γ δ TCR的功能 T细胞在肠上皮的病理条件下，皮肤