IMMUNE POTENTIAL OF ANIMAL LACKING CLASS IA MOLECULES

该提案研究了CD 8 T细胞在免疫应答中的独特功能， 传染源我们的主要重点是CDST细胞在先天性免疫反应中的作用， 单核细胞增生李斯特菌（Listeria monocytogenes，LM）我们最近证明，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抗LM的先天应答。进一步 将“先天性”CDS T细胞转移到干扰素-γ缺陷小鼠中可保护它们免受LM感染。我们 提出CDST细胞在INF-γ介导的先天性应答中起主要作用。 在第一个目的中，我们研究了CDS与NK细胞在提供这种类型的先天性免疫应答方面的相对效力。 保护我们假设效应CDS T记忆细胞（TFM）。已经被证明可以演奏小调 在获得性免疫应答中的作用在先天性应答中起着重要作用，并将测试这一点。 假说.在第二个目标中，我们将研究CDS中央记忆细胞（TOM）的定位。透射电镜ANC 脾脏和肝脏中LM感染部位的MK细胞。我们将使用缺乏CCR 7结合趋化因子的小鼠！ CCL-19和CCL-21）来评估这种趋化因子-受体相互作用如何影响先天性巨噬细胞中的CDS T细胞。 反应我们还将利用新的表达Thy-1.1的BAG转基因小鼠作为IFN-γ的报告基因 分泌以原位检查分泌IFN-γ的CDS和NK细胞。在第三个目标中，我们将确定 CD 4 T细胞在将幼稚CD 4 T细胞极化为Th 1亚群中的作用。在第四个目标中，我们将通过 微阵列分析显示，由IL-12/18（先天性）激活的CDS T细胞的基因展示与由IL-12/18（先天性）激活的CDS T细胞的基因展示相比， 通过TcR激活（自适应）。总而言之，本提案将增加重要的新信息， CD 8 T细胞在针对细胞内病原体的先天免疫应答中起作用。

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.