The role of CX3CR1+ CD4+ T cells during helminth infection

寄生蠕虫感染全球超过20亿人。它们造成严重的发病率和死亡率， 发展中国家，尤其是儿童。针对任何类型人类的有效疫苗 蠕虫感染一直难以捉摸，部分原因是对如何诱导保护性免疫缺乏了解。 对这些寄生虫的免疫力寄生蠕虫诱导CD4+ TH2驱动的免疫应答。这 这种反应不仅是驱逐寄生虫所必需的，而且也是修复由感染引起的组织损伤所必需的， 减轻慢性持久性导致的任何进一步病理。开发有效的疫苗， 蠕虫可能需要仔细了解CD4+记忆T细胞形成的机制， 功能某些CD4+和CD8+ T细胞亚群在免疫过程中将表达趋化因子受体CX3CR1。 炎症和感染。CD8+ T细胞上的CX3CR1表达可以帮助预测记忆表型。 病毒感染CX3CR1+ CD4+ T细胞在蠕虫诱导的2型免疫应答中的作用 感染完全未知。我们最近发现，CX3CR1+ CD4+ T细胞聚集在 受蠕虫感染影响的组织，但不包括引流淋巴结。在曼氏血吸虫病期间 感染CX3CR1+ CD4+ T细胞在肉芽肿形成期间在肝脏中积累。在日本圆线虫期间 巴西人感染后，这些细胞迅速积聚在肺部。该提案的目的是进一步 通过两个特定的目的来表征该CD4+ T细胞群体的表型和功能。在 第一个目的，我们将检验以下假设：在蠕虫感染期间，来自发炎组织的CX3CR1+ CD4+ T细胞 感染后可在运输至脾脏后分化为T滤泡辅助细胞。在第二个目标中，我们将 确定CX3CR1+ CD4+ T细胞是否有助于生殖中心形成、抗体应答和宿主免疫应答。 防止继发感染。总的来说，我们提出的研究将增加我们对 在2型免疫应答期间，蠕虫感染小鼠组织中的CD4+CX3CR1+细胞。这 对T细胞群体的了解很少，可能对支持抗体应答、寄生虫感染和免疫应答很重要。 驱逐、保护性免疫和组织修复。利用遗传命运作图和条件性耗竭 系统，我们可以彻底表征他们的表型和功能蠕虫感染。

Parasitic helminths infect over 2 billion people worldwide. They cause significant morbidity and mortality in developing areas of the world, especially among children. An effective vaccine against any type of human helminth infections has been elusive, partly because there is a poor understanding of how to induce protective immunity against these parasites. Parasitic helminths induce a CD4+ TH2 driven immune response. This response is necessary not only to expel the parasite, but also to repair tissue damage caused by infection and mitigate any further pathology resulting from chronic persistence. The development of an effective vaccine to helminths may require a meticulous understanding of the mechanism of CD4+ memory T cell formation and function. Certain subsets of CD4+ and CD8+ T cells will express the chemokine receptor CX3CR1 during inflammation and infection. CX3CR1 expression on CD8+ T cells can help predict memory phenotypes during viral infections. The role of CX3CR1+ CD4+ T cells during type-2 immune responses induced by helminth infection is completely unknown. We have recently found that CX3CR1+ CD4+ T cells accumulate in the tissues affected by helminth infections, but not in the draining lymph nodes. During Schistosoma mansoni infection CX3CR1+ CD4+ T cells accumulate in the liver during granuloma formation. During Nippostrongylus brasiliensis infection these cells rapidly accumulate in the lungs. The goal of this proposal is to further characterize the phenotype and function of this population of CD4+ T cells, through two specific aims. In the first Aim, we will test the hypothesis that CX3CR1+ CD4+ T cells from inflamed tissues during helminth infection can differentiate into T follicular helper cells after trafficking to the spleen. In the second Aim, we will determine if CX3CR1+ CD4+ T cells contribute to germinal center formation, antibody responses and host protection against secondary infection. Overall, the study we propose will increase our understanding of CD4+CX3CR1+ cells in the tissues of helminth infected mice, during a type-2 immune response. This population of T cells is poorly understood and may be important for supporting antibody responses, parasite expulsion, protective immunity and tissue repair. Utilizing genetic fate-mapping and conditional depletion systems, we can thoroughly characterize their phenotype and function during helminth infections.