The role of CD163L1 in CD8+ T cells

CD163L1 在 CD8 T 细胞中的作用

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要感染后，幼稚 CD8+ T 细胞分化为效应 T 细胞或记忆 T 细胞，这有助于消除尽管进行了数十年的研究，但仍不清楚为什么有些天真。 CD8+ T 细胞成为效应细胞并死亡，而其他细胞则存活并成为长寿的记忆细胞。经典模型假设 CD8+ T 细胞的单一谱系在然而，我们发表的工作和初步数据表明，CD8+ 存在不同的谱系。起始群体中的 T 细胞（胎儿来源的和成人来源的），是在不同的时间窗口中产生的该模型表明在感染过程中沿着不同的途径发育和分化。 CD8+ T 细胞区室内的分娩过程是由不同的个体发育谱系介导的，类似于 B 细胞亚群（B1a、B1b、B2），具有独特的功能，但与 B 细胞不同。领域，T 细胞领域缺乏有用的标记来识别成年小鼠中胎儿和成人来源的 CD8+ T 细胞，我们根据我们的初步数据和，仍然不完全了解他们行为的根本基础。发表的研究结果中，我们已经鉴定出一种清道夫受体（CD163L1），它在胎儿上特异性表达在目标 1 中，我们将确定是否会产生 CD8+ T 细胞并有助于其更快地发挥先天样功能。 CD163L1 是胎儿来源的 CD8+ T 细胞的标记物。在目标 2 中，我们将研究 CD163L1 如何改变功能。我们的建议有望开辟新的研究途径并推进我们的概念。了解 CD8+ T 细胞对感染的反应。