IMMUNE POTENTIAL OF ANIMAL LACKING CLASS IA MOLECULES

这项建议研究了CDS T细胞在免疫应答中的独特功能 感染剂。我们主要关注CDST细胞在先天免疫反应中所起的作用。 感染单核细胞增多性李斯特菌(Lm)我们最近证明了抗原非特异性CDS T 记忆细胞通过分泌干扰素-γ参与细胞因子驱动的针对LM的先天反应。进一步 将“天生的”CDS T细胞转移到干扰素缺乏的小鼠体内，可以保护它们免受LM的感染。我们 提示CDST细胞在干扰素-γ介导的先天免疫反应中起主要作用。 在第一个目标中，我们研究了CDS和NK细胞在提供这种类型的先天细胞方面的相对效力 保护。我们推测效应器CDS-T记忆细胞(TFM)。已经被证明可以扮演一个未成年人 获得性免疫反应在先天免疫反应中起重要作用 假设。在第二个目标中，我们将研究CDS中央记忆细胞(TOM)的定位。特姆。非国大 肝、脾Lm感染部位的MK细胞。我们将使用CCR7结合趋化因子缺陷的小鼠！ CCL-19和-21)，以评估这种趋化因子-受体相互作用如何影响先天CDS T细胞 回应。我们还将利用新的表达Thy-1.1的BAG转基因小鼠作为干扰素-γ的报告 原位检测细胞分泌干扰素-γ的CDS和NK细胞。在第三个目标中，我们将确定 CDS T细胞在极化NaI时有CD4T细胞向Th1亚群转化。在第四个目标中，我们将通过 基因芯片分析IL-12/18(天然)激活的CDS T细胞与未激活的CDS T细胞的基因表达 通过TCR激活(自适应)。总而言之，这项提案将增加关于如何 CDS T细胞在针对细胞内病原体的先天免疫反应中发挥作用。

This proposal investigates a unique function for CDS T cells in the immune response against infectious agents. Our major focus is on the role that CDST cells play in the innate immune response during infection with Listeria monocytogenes (LM). We recently demonstrated that antigen non specific CDS T memory cells participate in a cytokine driven innate response against LM by secreting interferon-y. Further ransfer of "innate" CDS T cells into interferon-y deficient mice protects them from infection with LM. We propose that CDST cells play a major role in the INF-y mediated innate response. In the first Aim we investigate the relative potency of CDS vs NK cells in providing this type of innate protection. We postulate that effector CDS T memory cells (TFM). which have been shown to play a minor role in the adaptive immune response play an important role in the innate response and will test thii hypothesis. In the second Aim we will examine the localization of CDS central memory cells (TOM). TEM. anc MK cells at sites of LM infection in spleen and liver. We will use mice deficient in CCR7 binding chemokine! CCL-19 and -21) to assess how this chemokine-receptor interaction affects CDS T cells in the innate response. We will also utilize new BAG transgenic mice that express Thy-1.1 as a reporter for IFN-y secretion to examine IFN-y secreting CDS and NK cells in situ. In the third Aim we will determine the role of CDS T cells in polarizing nai've CD4 T cells to the Th1 subset. In the fourth Aim we will examine by microarray analysis the gene display of CDS T cells that are activated by IL-12/18 (innate) vs those that are activated through the TcR (adaptive). In summary, this proposal will add important new information on how CDS T cells function in the innate immune response against intracellular pathogens.