GUT-DERIVED IMMUNE EFFECTOR CELLS

肠道来源的免疫效应细胞

• 批准号: 3233875
• 负责人: JOHN R KLEIN
• 金额: $ 12.37万
• 依托单位: UNIVERSITY OF TULSA
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-04-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3233875
• 关键词: MHC class I antigen; MHC class II antigen; T cell receptor; T lymphocyte; athymic mouse; cell differentiation; cell population study; clone cells; flow cytometry; gastrointestinal epithelium; gastrointestinal system; gene expression; immunoregulation; laboratory mouse; laboratory rabbit; laboratory rat; leukocyte activation /transformation; lymphocyte; monoclonal antibody; polymerase chain reaction; thymus; tissue mosaicism

This project is a continuation of studies of various immunobiological properties of murine intestinal intraepithelial lymphocytes (IEL), so as gain a better understanding of human IEL in immunity and disease. There are three major components. The first involves detailed studies of IEL ontogeny and thymus dependency using adult Fl --> parent athymic radiation chimeras. Experiments in athymic chimeras will evaluate the status, and expression, of T cell receptor (TCR) genes using the method of polymerase chain reaction to determine the location(s) (e.g., intestinal vs extraintestinal), and nature, of extrathymically-matured IEL; and to characterize TCR variable region usage(s). Early-lineage origins of BM-- derived IEL precursors will be studied in IEL repopulation experiments. The functional nature, and phenotypic properties, of endogenously (in situ) activated IEL, and the degree of antigen recognition and specificity of effector IEL will be studied in athymic chimeras. A second series of experiments, in thymus-bearing mice, will examine functionally-important phenotypically-defined IEL to determine how such components may be mechanistically important. Newly-described IEL subsets will be studied for immunoregulatory and/or effector properties. IEL expressing the gamma-delta TCR will be studied for antigen specificity, cytotoxic activity, and as a function of antigen exposure in normal and germ-free mice. IEL-specific monoclonal antibodies isolated in this laboratory will be used to delineate functionally- and/or developmentally-relevant IEL. The third series of experiments will explore the relationship of IEL with and intestinal epithelia as they relate to IEL development and immune function. These studies will examine intestinal MHC class I and II antigens, using in vivo blocking experiments with non-depleting monoclonal antibodies, to evaluate the role of MHC in IEL development or effector activation. Intestine-derived epithelial cell lines will be isolated for in vitro experiments of IEL immunoregulation. Known epithelium-derived cytokines (e.g., TGFbeta(1), and others) will be used in studies of early- and late-stage IEL maturation and regulation.

该项目是各种免疫生物学研究的延续。 小鼠肠上皮内淋巴细胞（IEL）的特性， 更好地了解人类IEL在免疫和疾病方面的作用。有 三大组成部分。第一个涉及IEL个体发育的详细研究 和胸腺依赖性。 在无胸腺嵌合体中的实验将评估其状态和表达， T细胞受体（TCR）基因的聚合酶链反应 确定位置的反应（例如，肠道vs 肠外）和性质，胸腺外成熟IEL;以及 表征TCR可变区使用。BM的早期谱系起源 将在IEL再增殖实验中研究衍生的IEL前体。的 功能性质和表型特性，内源性（原位） 激活的IEL，以及抗原识别和特异性的程度， 将在无胸腺嵌合体中研究效应子IEL。 第二组实验，在胸腺小鼠中，将检查 功能重要的表型定义的IEL，以确定如何， 部件在机械上可能是重要的。新描述的IEL子集 将研究其免疫调节和/或效应物特性。IEL 将研究表达γ-δ TCR的抗原特异性， 细胞毒活性，并作为正常和 无菌小鼠IEL特异性单克隆抗体分离， 实验室将用于描述功能-和/或 与发展相关的IEL。 第三系列实验将探讨IEL与 和肠上皮细胞，因为它们与IEL的发育和免疫有关 功能这些研究将检查肠道MHC I类和II类 使用非消耗性单克隆抗体的体内阻断实验 抗体，以评估MHC在IEL发育或效应子中的作用。 activation.将分离肠源性上皮细胞系， IEL免疫调节的体外实验。已知上皮来源 细胞因子（例如，TGF β（1）和其他）将用于早期- 以及晚期IEL成熟和调节。