INITIATION OF T CELL IMMUNE RESPONSES IN GUT MUCOSA

我们建议详细研究以下机构的参与和职能 肠相关淋巴组织(GALT)中的不同淋巴样细胞 在粘膜T细胞介导的免疫应答中的作用 迟发型超敏反应与细胞介导的淋巴溶解 (慢性粒细胞白血病)口服半抗原。我们选择了学习 这两种T细胞介导的免疫反应不仅是因为 对它们在粘膜和粘膜中的存在知之甚少 肠道的其他有组织的淋巴组织，但也因为 这些反应可能提供对致病原的局部保护。 肠道病毒、细菌和寄生虫。 我们将确定半抗原发展的时间进程 GALT中特异的水解酶和细胞毒性T淋巴细胞(CTL) 由于在形态和上皮细胞动力学方面的变化发生在 给小鼠灌胃半抗原后的小鼠小肠。无论是 这两种反应的动力学和大小是可以改变的 将通过用环磷酰胺对动物进行预处理来确定 或不止一次喂食半抗原。提纯的能力 从GALT中分离的免疫T细胞过继转移水解酶 发展半抗原诱导的T细胞增殖，并产生 将检测迁移抑制因子(MIF)。是否T GALT中存在辅助体内DH诱导的辅助性细胞 以半抗原喂养的动物将通过它们的生产能力进行检查 半抗原特异性辅助因子在体内发育中的作用 回应。Galt-TdH表面的表型标记 和TH(DH)、半抗原特异性和任何遗传限制 他们的功能将被审查。 Galt淋巴细胞产生CTL和 产生淋巴因子(白介素2和分化因子) 在体外产生CTL所需的条件是 评估过了。半抗原特异性CTL前体细胞的频率 不同淋巴系人群(P-CTL)和TH分泌IL-2的研究 GALT的含量将通过有限稀释分析(LDA)来测定。 这里提出的试验性工作将使我们能够获得 有关GALT淋巴细胞功能的信息 粘膜T细胞介导的反应的诱导可能 提供针对饮食和致病抗原的保护，或 可能对肠道有不良影响。

We propose to examine in detail the participation and function of different lymphoid cells in gut associated lymphoid tissues (GALT) in the development of mucosal T cell-mediated responses of delayed hypersensitivity (DH) and cell-mediated lympholysis (CML) to orally administered hapten. We have chosen to study these two T cell-mediated immune responses not only because very little is known about their occurrence at the mucosal and other organized lymphoid tissues of the gut, but also because these responses may provide local protection against pathogenic enteric viruses, bacteria, and parasites. We will determine the time course of development of hapten specific DH and cytotoxic T lymphocytes (CTL) in GALT as well as changes in morphology and epithelial cell kinetics that occur in small intestine after feeding hapten to the mice. Whether the kinetics and the magnitude of these two responses can be altered will be determined by pretreating animals with cyclophosphamide or feeding the hapten more than once. The ability of purified immune T cells isolated from GALT to adoptively transfer DH, to develop hapten induced T cell proliferation, and to produce migration inhibition factor (MIF) will be examined. Whether T helper cells that assist in vivo DH induction are present in GALT of hapten-fed animals will be examined by their ability to produce hapten specific helper factor that aids development of in vivo DH response. The phenotypic markers on the surface of GALT TDH and TH(DH), hapten specificity and any genetic restriction of their function will be examined. The capacity of the GALT lymphocytes to generate CTLs and produce lymphokines (interleukin 2 and differentiation factor) that are required for the generation of CTLs in vitro will be assessed. The frequencies of precursors of hapten specific CTLs (p-CTL) and TH secreting IL2 among various lymphoid populations of GALT will be determined by limiting dilution analysis (LDA). The experimental work proposed here will allow us to acquire information about functional capabilities of GALT lymphocytes in the induction of mucosal T cell-mediated responses that may provide protection against dietary and pathogenic antigens or that may have adverse effects on the intestine.