Functional Biology Of T Cells

T 细胞的功能生物学

• 批准号: 7592219
• 负责人: Ronald N Germain
• 金额: $ 86.94万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7592219
• 关键词: Adjuvant; Animals; Antigen-Presenting Cells; Antigens; Autoimmune Process; Autoimmune Responses; Bacteria; Biology; Blood; CD8B1 gene; Cell Communication; Cell Lineage; Cell division; Cells; Data; Dendritic Cells; Drug or chemical Tissue Distribution; Effector Cell; Equilibrium; Evaluation; Frequencies; Future; Generations; Host Defense; Imaging Techniques; Immune; Immune response; Immune system; Infection; Invaded; Invasive; Left; Leukocytes; Lymphocyte; Lymphoid; Lymphoid Tissue; Maintenance; Mediating; Membrane; Memory; Methods; Movement; Natural Killer Cells; Normal tissue morphology; Organism; Pathology; Peripheral; Play; Property; Protozoa; Research; Resolution; Rest; Role; Route; Scheme; Signal Transduction; Site; Source; Spleen; T-Cell Proliferation; T-Lymphocyte; Tissues; Vaccination; Vaccine Design; Virus; Work; cancer cell; cell motility; fungus; insight; lymph nodes; man; pathogen; response

White blood cells called T lymphocytes play critical roles in immune defense against viruses, bacteria, fungi, protozoa, and cancer cells. In the unactivated state, these cells circulate in the blood and accumulate in lymphoid tissues such as lymph nodes and spleen. Upon encounter with foreign materials (antigens) on the membranes of specialized antigen presenting cells (dendritic cells), these resting T-cells become activated, undergo numerous cell divisions, and differentiate into effector cells. The effector cells leave the lymphoid tissues and blood, entering sites of infection to combat pathogens. They can also invade normal tissues where their activity can cause autoimmune pathology. After elimination of an infecting organism, most of the activated T-cells die, but some remain as memory cells, to provide a more rapid and vigorous response if the same pathogen is encountered in the future. Recent work has suggested that this general scheme applies to both CD4 and CD8 T-cells, but that there are also important differences in the signals that control the extent of proliferation and the survival of memory cells for these two T-cells lineages. Furthermore, there are also data suggesting that memory cells may be of more than one type, with some recirculating in lymphoid compartments and others patrolling peripheral tissues. The former may provide the major source of new cells upon re-infection, whereas the latter may mediate the earliest effector response to the infection. The proper balance of both types may be critical for effective T-cell mediated host defense. Other lymphocytes such as NK cells and regulatory T cells contribute to both the enhancement and suppression of these T cell responses through direct and indirect means. This project attempts to gain a quantitative understanding of the activation, differentiation, migration, cell-cell interaction, memory status, and reactivation properties of both CD4 and CD8 T-cells. Issues such as the route, amount, and frequency of antigen exposure, as well as the presence or absence of adjuvants that stimulate the innate immune system, are being studied for their effects on the generation and tissue distribution of effector and memory CD4 and CD8 T-cells. The movement of activated T-cells into non-lymphoid tissues is being analyzed using both conventional cellular immunological methods and newer imaging techniques that allow high resolution dynamic observation of how cells migrate, interact, and carry out their effector functions. Through this research, a better understanding of lymphocyte dynamics during an immune response to infection or after vaccination or during an autoimmune response will be established. These new insights can contribute to the more effective design of vaccines and to strategies for the amelioration of autoimmune processes.

称为T淋巴细胞的白细胞在针对病毒，细菌，真菌，原生动物和癌细胞的免疫防御中起关键作用。在未激活状态下，这些细胞在血液中循环并积聚在淋巴结和脾脏等淋巴组织中。在特殊抗原呈递细胞（树突状细胞）的膜上遇到异物（抗原）后，这些静止的T细胞被激活，经历了许多细胞分裂，并分化为效应细胞。效应细胞离开淋巴组织和血液，进入感染部位，以打击病原体。它们还可以入侵正常的组织，其中其活性会引起自身免疫性病理。消除感染生物体后，大多数活化的T细胞死亡，但有些仍是记忆细胞，如果将来遇到相同的病原体，则可以提供更快和剧烈的反应。最近的工作表明，这种一般方案适用于CD4和CD8 T细胞，但在控制这两个T细胞谱系的增殖程度和存储细胞存活的信号上也存在重要差异。此外，还有数据表明记忆细胞可能不止一种类型，其中一些在淋巴室中循环，而另一些则在周围组织巡逻。前者可能会在重新感染后提供新细胞的主要来源，而后者可以介导最早的效应子对感染的反应。两种类型的适当平衡对于有效的T细胞介导的宿主防御可能至关重要。其他淋巴细胞（例如NK细胞和调节性T细胞）通过直接和间接手段促进了这些T细胞反应的增强和抑制。该项目试图对CD4和CD8 T细胞的激活，分化，迁移，细胞 - 细胞相互作用，记忆状态和重新激活的特性获得定量理解。正在研究抗原暴露的路线，数量和频率，以及刺激先天免疫系统的佐剂的存在或不存在，以对它们对效应子的产生和组织分布以及记忆CD4和CD8 T细胞的影响。正在使用常规的细胞免疫学方法和更新的成像技术分析活化的T细胞向非淋巴组织的运动，这些方法允许对细胞如何迁移，相互作用和执行其效应子功能进行高分辨率的动态观察。通过这项研究，将建立对感染免疫反应或疫苗接种后或自身免疫反应期间的淋巴细胞动力学的更好理解。这些新的见解可以有助于更有效的疫苗设计，并有助于改善自身免疫工艺的策略。