The role of CD163L1 in CD8+ T cells

CD163L1 在 CD8 T 细胞中的作用

• 批准号: 10593557
• 负责人: ANDREW W GRIMSON
• 金额: $ 23.86万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-11-10 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10593557
• 关键词: Adopted; Adult; Antigens; B-Lymphocytes; Behavior; Bone Marrow; CD6 antigen; CD8-Positive T-Lymphocytes; Cattle; Cell Compartmentation; Cells; Complex; Cues; Data; Development; Environment; Extracellular Domain; Family suidae; Fetal Liver; Genes; Hematopoietic stem cells; Immune system; Immunity; Immunology; Impairment; Infection; Inflammation; Injections; Life; Ligand Binding; Link; Maps; Mediating; Memory; Modeling; Mus; Neonatal; Pathway interactions; Pattern; Peripheral; Phenotype; Play; Population; Proteins; Publishing; Reagent; Reporter; Research; Role; SRCR proteins; Sheep; Signal Transduction; System; T cell differentiation; T cell response; T memory cell; T-Cell Activation; T-Lymphocyte; Thymus Gland; Vaccines; Work; aged; crosslink; fetal; fetus cell; innovation; interest; mature animal; member; mouse model; novel; pathogen; progenitor; protein protein interaction; receptor; response; scavenger receptor; selective expression; tool; transcriptomic profiling; vaccination outcome

Project Summary / Abstract Following infection, naïve CD8+ T cells differentiate into effector or memory T cells, which help to eliminate pathogens and maintain long-term immunity. Despite decades of research, it is still not clear why some naïve CD8+ T cells become effectors and die, whereas others survive and become long-lived memory cells. The canonical model posits that a single lineage of CD8+ T cells undergoes phenotypic diversification after stimulation. However, our published work and preliminary data show that there are separate lineages of CD8+ T cells (fetal-derived and adult-derived) in the starting population, which are made during distinct windows of development and differentiate along different pathways during infection. This model suggests that the division of labor within the CD8+ T cell compartment is mediated by distinct ontogenetic lineages, similar to subpopulations of B cells (B1a, B1b, B2), which have unique functional capabilities. However, unlike the B cell field, the T cell field lacks a useful marker to identify fetal- and adult-derived CD8+ T cells in adult mice, and we still do not fully understand the underlying basis for their altered behavior. Based on our preliminary data and published findings, we have identified a scavenger receptor (CD163L1) that is specifically expressed on fetal- derived CD8+ T cells and contributes to their more rapid innate-like functions. In Aim 1, we will establish whether CD163L1 is a marker for fetal-derived CD8+ T cells. In Aim 2, we will examine how CD163L1 alters the functions of CD8+ T cells. Our proposal is expected to open up new avenues of research and advance our conceptual understanding of the CD8+ T cell response to infection.

项目总结/摘要 感染后，幼稚的CD 8 + T细胞分化为效应或记忆T细胞，这有助于消除 保持长期免疫力。尽管经过了几十年的研究，仍然不清楚为什么一些天真的人 CD 8 + T细胞成为效应细胞并死亡，而其他细胞存活并成为长寿的记忆细胞。的 经典模型假定，单一谱系的CD 8 + T细胞经历表型多样化后， 刺激.然而，我们发表的工作和初步数据表明，CD 8+细胞有不同的谱系， 起始群体中的T细胞（胎儿来源的和成人来源的），其在不同的免疫窗期间产生。 在感染过程中沿着不同的途径发育和分化。这个模型表明， CD 8 + T细胞区室中的分娩由不同的个体发生谱系介导，类似于 B细胞亚群（B1 a、B1 B、B2），其具有独特的功能能力。然而，与B细胞不同， T细胞领域缺乏一个有用的标记来识别成年小鼠中胎儿和成人来源的CD 8 + T细胞，我们 仍然没有完全理解他们改变行为的潜在基础。根据我们的初步数据， 我们发现了一种清道夫受体（CD 163 L1），它特异性表达于胎儿- CD 8 + T细胞是CD 8 + T细胞的衍生物，并有助于其更快速的先天性功能。在目标1中，我们将确定 CD 163 L1是胎儿来源的CD 8 + T细胞的标志物。在目标2中，我们将研究CD 163 L1如何改变这些功能。 CD 8 + T细胞我们的建议有望开辟新的研究途径， 了解CD 8 + T细胞对感染的反应。