CD4 T Cell Response to Salmonella

描述（由申请人提供）：先天和适应性免疫系统对微生物的识别可以导致感染的解决和长期免疫的发展。许多微生物病原体通过穿透肺、肠和泌尿生殖道的粘膜表面进入宿主体内。然而，对粘膜表面微生物病原体的免疫反应的诱导尚不清楚。该建议的具体目标是：目标1。鉴定体内呈现沙门氏菌抗原的细胞类型，以验证淋巴树突状细胞激活沙门氏菌特异性CD4 T细胞的假设。这些研究将直接检查体内沙门氏菌编码抗原的呈现，以验证淋巴树突状细胞在口腔感染后负责激活沙门氏菌特异性CD4 T细胞的假设。目标2。检查脾脏中沙门氏菌特异性T细胞的活化，并确定该器官中T细胞无反应的机制。我们的初步数据表明，尽管细菌在脾脏中进行复制，但沙门氏菌特异性CD4 T细胞在脾脏中的激活效率不高。我们假设，细菌在脾红髓的位置物理分离抗原沙门氏菌特异性T细胞。这将使用一种新的沙门氏菌特异性TCR过继转移系统进行测试。目标3。检测CD4T细胞的分化和迁移，以验证效应/记忆T细胞在沙门氏菌感染后不能有效产生的观点。我们的初步数据表明，口腔感染后沙门氏菌特异性T细胞的非淋巴迁移缺陷。我们假设，由于局部粘膜启动环境，T细胞效应功能不能有效地发展。这一问题将通过检测口腔感染后沙门氏菌特异性T细胞的效应细胞因子产生和非淋巴细胞迁移来检验。这些研究将为粘膜病原体免疫的发展提供新的见解。

DESCRIPTION (provided by applicant): The recognition of microbes by the innate and adaptive immune system can lead to the resolution of infection and development of long-lived immunity. Many microbial pathogens gain entry to the host by penetrating mucosal surfaces of the lung, intestine and genito-urinary tract. However, the induction of immune responses to microbial pathogens at mucosal surfaces is not well understood. The specific aims of the proposal are: Aim 1. To identify the cell types that present Salmonella antigens in vivo in order to test the hypothesis that lymphoid dendritic cells activate Salmonella-specific CD4 T cells. These studies will directly examine the presentation of a Salmonella encoded antigen in vivo, in order to test the hypothesis that lymphoid dendritic cells are responsible for activating Salmonella-specific CD4 T cells after oral infection. Aim 2. To examine Salmonella-specific T cell activation in the spleen and define mechanisms that account for T cell unresponsiveness in this organ. Our preliminary data indicate that Salmonella-specific CD4 T cells are inefficiently activated in the spleen, despite bacterial replication in this organ. We hypothesize that the location of bacteria in the spleen red pulp physically separates antigen from Salmonella-specific T cells. This will be tested using a novel Salmonella-specific TCR adoptive transfer system. Aim 3. To examine CD4T cell differentiation and migration in order to test the idea that effector/memory T cells are not efficiently generated after Salmonella infection. Our preliminary data indicate a defect in non-lymphoid migration of Salmonella-specific T cells following oral infection. We hypothesize that T cell effector functions do not develop efficiently, due to the local mucosal priming environment. This issue will be tested by examining the effector cytokine production and non-lymphoid migration of Salmonella-specific T cell after oral infection. These studies will provide new insight into the development of immunity to mucosal pathogens.