EXPRESSION OF SURFACE MARKERS ON T CELLS IN TRANSGENIC MOUSE MODEL

将产生在以下条件下表达人Thy-1的转基因小鼠： 小鼠IFN-γ启动子和小鼠Thy-1.1的控制 鼠IL-4启动子的控制。这些转基因将被引入 转化为许多鼠Thy-1.2+菌株。因为 使用启动子，人Thy-1将在表达Thy-1的TH 1 T细胞中表达。 IFN-γ和鼠Thy-1.1将在表达IL-1的TH 2细胞中表达。 4. 人Thy-1和鼠Thy-1.1两者都可能是 在THO细胞中表达。 这种双重积极性将成为一个标志， THO子集。 利用适当的单克隆抗体，这些 转基因小鼠将为检测提供独特的细胞表面标记 TH 1、TH 0和TH 2 T细胞亚群。（CD 8和CD 8的单克隆抗体） 需要NK 1来检测预期的少量CD 8 + T细胞 和也表达IFN-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 紧张的背景。 转基因也将被引入三个T 细胞受体转基因系，其表达特异于 髓鞘碱性蛋白肽和两种流感血凝素肽 由CD 4和CD 8 T细胞受体识别。 的存在 这些近交系中的报告基因转基因将允许分析 TH 1，THO和TH 2 T细胞亚群在正常免疫中的作用 在各种免疫条件下以及在自身免疫中的反应 在NOD小鼠中，在实验性过敏性脑脊髓炎（EAE）中， 在（B10.PL x SJL）F1小鼠中，以及在 NZB x NZW小鼠和MRL-lpr/lpr小鼠。 同样， 转基因将允许分析TH 1和TH 2 T细胞亚群， 注射了T细胞受体被阻断的肽的转基因小鼠 转基因，并将允许研究的相对诱导 TH 1和TH 2细胞亚群中的凋亡无反应性和缺失。在 此外，这些报告基因/转基因小鼠系将允许 分析T细胞亚群在多种免疫应答中的作用 条件，并将提供给其他研究人员在这方面， 计划项目以及其他研究人员在这方面和其他 机构职能体系 最终，这些转基因小鼠提供了 验证T细胞亚群分化的非常有效的范例， 最初由Coffmann和Mossmann提出。

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.