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.

项目摘要/摘要 感染后，幼稚的CD8+T细胞分化为效应T细胞或记忆T细胞，这有助于消除 病原体和维持长期免疫力。尽管进行了几十年的研究，但仍不清楚为什么一些天真的 CD8+T细胞成为效应器并死亡，而其他细胞存活并成为长期记忆细胞。这个 典型模型假设CD8+T细胞的单一谱系经历了表型多样化 刺激。然而，我们发表的工作和初步数据表明，CD8+有不同的谱系 起始群体中的T细胞(胎儿来源和成人来源)，它们是在不同的 在感染过程中沿着不同的途径发育和分化。这一模型表明， CD8+T细胞内的劳动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。然而，与B细胞不同 在成年小鼠中，T细胞区缺乏一个有用的标记来识别胎儿和成人来源的CD8+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和 已发表的研究发现，我们发现了一种清道夫受体(CD163L1)，它特异地表达于胎儿- 来自CD8+T细胞，并有助于其更快的先天功能。在目标1中，我们将确定 CD163L1是胎儿CD8+T细胞的标志物。在目标2中，我们将研究CD163L1如何改变函数 CD8+T细胞。我们的建议有望开辟研究的新途径，并推动我们的概念 了解CD8+T细胞对感染的反应。