DC-CD4 interactions in Th2 differentiation

CD4+ T细胞的效应功能是对蠕虫（如滴虫和血吸虫）的免疫应答所必需的。CD4+ T细胞被主要组织相容性复合体（MHC） II类分子激活，这些分子由造血抗原呈递细胞（ARC）、树突状细胞、巨噬细胞和B细胞表达。在寄生虫的CD4+ T细胞依赖性控制过程中，个体MHC类l阳性apc的特定需求尚未完全阐明。我们开发了转基因CD11c/ β (b)小鼠，其中MHC II类l-Ab表达特异性针对dc；这种II类表达模式足以发展对名义抗原的原发性Th1反应和控制皮下利什曼原虫感染。相比之下，树突状细胞抗原呈递在Th2反应发展中的充分性尚不清楚。例如，B细胞是对名义抗原和寄生抗原产生Th2反应和控制胃肠道线虫（Trichuris muris）所必需的。我们建议利用CD11c/Abeta(b)模型来检验MHC类ll阳性dc对CD4+ T细胞在Th2反应产生中的抗原呈递的充分性。

The effector functions of CD4+ T cells are required for the immune response to helminths such as Trichuris and Schistosoma. CD4+ T cells are activated by major histocompatibility complex (MHC) class II molecules expressed by the hematopoietic antigen presenting cells (ARC), dendritic cells, macrophages, and B cells. The specific requirement for individual MHC class ll-positive APCs during CD4+ T cell-dependent control of parasites has not been fully elucidated. We have developed transgenic CD11c/Abeta(b) mice in which MHC class II l-Ab expression is targeted specifically to DCs; this pattern of class II expression is sufficient for development of primary Th1 responses to nominal antigen and control of subcutaneous Leishmania infection. In contrast, the sufficiency of dendritic cell antigen presentation in the development of Th2 responses is less clear. For example, B cells are required for the generation of Th2 responses to nominal and parasitic antigens and control of the gastrointestinal nematode, Trichuris muris. We propose to utilize the CD11c/Abeta(b) model to examine the sufficiency of antigen presentation by MHC class ll-positive DCs to CD4+ T cells in the generation of Th2 responses. We have three Specific Aims. In Specific Aim I, we will examine Th2 responses to the model antigens, ovalbumin and Schistosomal egg antigen. In Specific Aim II, we will ask if class ll-dependent interactions between DC and CD4+ T cells drive resistance to Trichuris muris nematode infection. Finally, we will ask if DC antigen presentation regulates the switch from Th1 to Th2 polarization which occurs during the immune response to Schistosoma mansoni. These pilot experiments will determine if DC-dependent antigen presentation generates protective antigen-specific immune responses against parasitic infections and will elucidate pathways to target in vaccine development.