Trafficking & role of effector memory CD8T cell subsets in small intestine

人口贩卖

• 批准号: 8904663
• 负责人: Jason M Schenkel
• 金额: $ 4.28万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2016-05-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8904663
• 关键词: Adoptive Transfer; CC chemokine receptor 7; CCL19 gene; CCL21 gene; CCR9 gene; CD8-Positive T-Lymphocytes; CD8B1 gene; Cell physiology; Cells; Cessation of life; Characteristics; Classification; Data; Enteral; Flow Cytometry; Generations; Health; Heterogeneity; Home environment; Hospitalization; Immune response; Immunobiology; Immunofluorescence Microscopy; Infection; Inflammation; Knowledge; Listeria monocytogenes; Lymph; Lymphatic; Lymphoid; Lymphoid Tissue; Memory; Mesentery; Mind; Mission; National Institute of Diabetes and Digestive and Kidney Diseases; Natural Killer Cells; Organ; Pattern; Phenotype; Population; Reporting; Role; SELL gene; Selectins; Site; Small Intestines; Stable Populations; T cell response; T memory cell; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Time; Tissues; Vaccine Design; Viral; Viral Gastroenteritis; base; cell motility; chemokine receptor; cytokine; cytotoxic; gastrointestinal infection; in vivo; lymph nodes; novel; pathogen; receptor; response; terminally differentiated effector memory (TEM) T cells; therapeutic vaccine; trafficking; vaccine development

DESCRIPTION (provided by applicant): Intracellular enteric infections are a global problem resulting in millions of hospitalizations and deaths every year. CD8 T cells are potent cytotoxic cells that control intracellular infection, and as such, represent a potential population to targetfor therapeutics and vaccine development. With this in mind, considerable characterizations, encompassing many aspects of CD8 T cell immunobiology, have resulted in substantial increases in our general understanding of CD8 T cell function. Up until recently, the paradigm for memory CD8 T cell function upon pathogen challenge centered on the hypothesis that memory CD8 T cell responses were predominantly generated within secondary lymphoid tissue. However, newer reports have highlighted important functions of memory CD8 T cells outside of secondary lymphoid tissue. For instance, it has recently been shown that memory CD8 T cells within nonlymphoid tissues provide important and potent early responses to local pathogen challenge. The mechanism by which this occurs is still not entirely understood, nor is it known how these responses are related to ones generated by CD8 T cells outside of the infected tissue. Moving forward, it will be critical to understand whether these responses within infected tissues operate in cooperative versus parallel manners with CD8 T cells outside of the infected site. The central hypothesis of this proposal is that there exist multiple populations of memory CD8 T cells outside of tissues that differentially migrate into the small intestine under homeostatic conditions and during states of inflammation. Further, these memory CD8 T cells may provide an important, early wave of cytotoxic responses within the small intestine. Therefore, my specific aims will 1) determine the functionality and importance of these different populations in response to pathogen challenge; 2) determine the stability and trafficking patterns of these different populations of CD8 T cell memory. This proposal supports the mission of the NIDDK because it focuses understanding memory CD8 T cell responses to intracellular gastrointestinal infections. With a better understanding of memory CD8 T cell function in the small intestine, could provide important information for rational vaccine design targeting CD8 T cells.

描述（由申请人提供）：细胞内肠道感染是一个全球性问题，每年导致数百万人住院和死亡。 CD8 T 细胞是控制细胞内感染的有效细胞毒性细胞，因此代表了治疗和疫苗开发的潜在目标群体。考虑到这一点，涵盖 CD8 T 细胞免疫生物学许多方面的大量表征已经导致我们对 CD8 T 细胞功能的一般理解大幅增加。直到最近，记忆 CD8 T 细胞在病原体攻击后发挥功能的范式主要集中在这样的假设上：记忆 CD8 T 细胞反应主要在次级淋巴组织内产生。 However, newer reports have highlighted important functions of memory CD8 T cells outside of secondary lymphoid tissue.例如，最近的研究表明，非淋巴组织内的记忆 CD8 T 细胞对局部病原体的攻击提供了重要而有效的早期反应。这种现象发生的机制尚不完全清楚，也不知道这些反应与受感染组织外的 CD8 T 细胞产生的反应有何关系。展望未来，了解感染组织内的这些反应是否与感染部位外的 CD8 T 细胞以合作或平行的方式运作至关重要。该提议的中心假设是，组织外存在多个记忆 CD8 T 细胞群，它们在稳态条件下和炎症状态下有差异地迁移到小肠中。 Further, these memory CD8 T cells may provide an important, early wave of cytotoxic responses within the small intestine. Therefore, my specific aims will 1) determine the functionality and importance of these different populations in response to pathogen challenge; 2) determine the stability and trafficking patterns of these different populations of CD8 T cell memory.该提案支持 NIDDK 的使命，因为它的重点是了解记忆 CD8 T 细胞对细胞内胃肠道感染的反应。更好地了解小肠中记忆 CD8 T 细胞的功能，可以为针对 CD8 T 细胞的合理疫苗设计提供重要信息。