EXPRESSION OF SURFACE MARKERS ON T CELLS IN TRANSGENIC MOUSE MODEL

将产生表达人Thy-1的转基因小鼠 小鼠干扰素-γ启动子和小鼠Thy-1.1基因的调控 小鼠IL-4启动子的调控。这些转基因将被引入 转化成许多小鼠Thy-1.2+的菌株。因为 使用启动子，人Thy-1将在TH1T细胞中表达，表达 干扰素-γ和小鼠Thy-1.1将在表达IL-1的TH2细胞中表达 4.人类Thy-1和小鼠Thy-1.1都有可能成为 在Tho细胞中表达。然后，这种双重肯定将成为 THO子集。利用适当的单抗，这些 转基因小鼠将为检测提供独特的细胞表面标记 TH1、THO和TH2型T细胞亚群。(抗CD8和 需要NK1来检测预期的少量CD8+T细胞 以及也表达干扰素-γ的NK细胞)。 然后将这些报告基因转基因导入BALB/c， B10.D2，NOD，NOD.A-beta-d，NOD.A-beta-g7.PD，B10.PL，NZB。MRL近交系 拉开背景。转基因也将被引入到三个T 表达特异性T细胞受体的细胞受体转基因株系 髓鞘碱性蛋白肽和两种流感血凝素多肽 由CD4和CD8 T细胞受体识别。出席会议的人 这些近交系中的报告基因转基因将允许进行分析 TH1、THO和TH2型T细胞亚群在正常免疫中的作用 在各种免疫条件下的反应，以及在自身免疫中 在NOD小鼠中，在实验性变态反应性脑脊髓炎(EAE)中 (B10.PL x SJL)F1小鼠，以及在 NZB×NZW小鼠和MRL-LPR/LPR小鼠。以类似的方式， 转基因将使分析TH1和TH2 T细胞亚群成为可能 给转基因小鼠注射T细胞受体结合的多肽 转基因并将允许研究相对诱导性 TH、L和TH2型细胞亚群中的细胞凋亡、无能和缺失。在……里面 此外，这些报告基因/转基因小鼠品系将允许 T细胞亚群在多种免疫反应中的作用分析 条件，并将向此案的其他调查人员提供 计划项目以及本项目和其他项目中的其他调查人员 机构。最终，这些转基因小鼠提供了一种可能性 验证T细胞亚群分化非常有效的范例 最初是由Coffmann和Mossmann提出的。

Transgenic mice will be produced which express human Thy-1 under the control of the murine IFN-gamma promoter and murine Thy-1.1 under the control of the murine IL-4 promoter. These transgenes will be introduced into a number of strains which are murine Thy-1.2+. Because of the promoters used, human Thy-1 will be expressed in TH 1 T cells expressing IFN-gamma and murine Thy-1.1 will be expressed in TH2 cells expressing IL- 4. It is possible that both human Thy-1 and murine Thy-1.1 will be expressed in THO cells. This double positivity will then be a marker for the THO subset. Utilizing the appropriate monoclonal antibodies, these transgenic mice will provide unique cell surface markers for the detection of the TH1, THO and TH2 T cell subsets.(monoclonal antibodies for CD8 and NK1 will be required to detect the expected small number of CD8+ T cells and NK cells which also express IFN-gamma). These reporter gene transgenes will then be introduced into the BALB/c, B10.D2, NOD, NOD.A-beta-d, NOD.A-beta-g7.PD, B10.PL, NZB. MRL inbred strain backgrounds. The transgenes will also be introduced into three T cell receptor transgenic lines expressing T cell receptor specific for a myelin basic protein peptide and two influenza hemagglutinin peptides recognized by a CD4 and a CD8 T cell receptor. The presence of the reporter gene transgenes in these inbred strains will permit an analysis of the role of the TH1, THO, and TH2 T cell subsets in the normal immune response in a variety of immunizing conditions, and in the autoimmunity seen in the NOD mouse, in experimental allergic encephalomyelitis (EAE) in the (B10.PL x SJL)F1 mouse, and in the autoimmune syndromes seen in the NZB x NZW mouse and the MRL-lpr/lpr mouse. In a similar manner, the transgenes will permit the analysis of TH1 and TH2 T cell subsets in transgenic mice injected with the peptide for which the T cell receptor is transgenic and will permit a study of the relative inducibility of apoptosis anergy and deletion in the TH l and TH2 cell subsets. In addition, these reporter gene/transgenic mouse lines will permit an analysis of the role of T cells subsets in a wide variety of immune conditions and will be made available to other investigators in this program project as well as to other investigators in this and other institutions. Ultimately, these transgenic mice offer the possibility of validating the very productive paradigm for T cell subset differentiation initially proposed by Coffmann and Mossmann.