INITIATION OF T CELL IMMUNE RESPONSES IN GUT MUCOSA

我们建议详细研究 肠相关淋巴组织（GALT）中的不同淋巴细胞 在粘膜T细胞介导的反应的发展中， 迟发型超敏反应（DH）和细胞介导的淋巴细胞溶解 (CML)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 关于它们在粘膜中的发生知之甚少， 肠道的其他有组织淋巴组织，但也因为 这些反应可以提供局部保护， 肠道病毒、细菌和寄生虫。 我们将确定半抗原形成的时间过程 GALT中特异性DH和细胞毒性T淋巴细胞（CTL 由于在细胞内发生的形态学和上皮细胞动力学的变化， 给小鼠喂食半抗原后的小肠。 是否 这两种反应的动力学和大小可以改变 将通过用环磷酰胺预处理动物来确定 或者不止一次地饲喂半抗原。 净化能力 从GALT分离的免疫T细胞过继性转移DH， 发展半抗原诱导的T细胞增殖，并产生 将检查迁移抑制因子（MIF）。 是否T 辅助体内DH诱导的辅助细胞存在于GALT中 的半抗原喂养的动物将检查他们的能力， 有助于体内DH形成的半抗原特异性辅助因子 反应 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， 将审查其职能。 GALT淋巴细胞产生CTL的能力和 产生淋巴因子（白细胞介素2和分化因子） 在体外产生CTL所需的细胞将被 评估。 半抗原特异性CTL的前体频率 （p-CTL）和TH分泌IL 2在不同的淋巴细胞群 将通过有限稀释分析（LDA）测定GALT。 这里提出的实验工作将使我们能够获得 关于GALT淋巴细胞功能的信息， 诱导粘膜T细胞介导的应答， 提供针对饮食和病原性抗原的保护，或者 可能会对肠道产生不良影响。

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.