CD4+ T Cell Receptors in Leishmaniasis

利什曼病中的 CD4 T 细胞受体

• 批准号: 7147430
• 负责人: Richard M Locksley
• 金额: $ 32.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-15 至 2008-06-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7147430
• 关键词: Animals; Biochemical; Biological Assay; Biology; CD4 Positive T Lymphocytes; Cells; Characteristics; Cytokine Receptors; Data; Disease; Effector Cell; Elements; Generations; Genes; Genetic Programming; Genetic Transcription; Green Fluorescent Proteins; Helper-Inducer T-Lymphocyte; Homeostasis; Host Defense; IL4 gene; Immune; Immune response; Immune system; Immunity; Immunology; In Vitro; Infection; Inflammatory; Interferon Type II; Interferons; Interleukin-4; Investigation; Learning; Leishmania major; Leishmaniasis; Link; Literature; Lymphoid; Mediating; Messenger RNA; Modeling; Molecular; Mouse Strains; Mus; Natural Killer Cells; Nippostrongylus; Organ; Outcome; Parasites; Pathway interactions; Peripheral; Phosphorylation; Physiological; Play; Polyribosomes; Population; Process; Production; Protein Secretion; Proteins; Receptor Signaling; Recruitment Activity; Regulation; Regulatory Element; Reporter; Reporting; Research; Rest; Shapes; Signal Pathway; Signal Transduction; Site; Stress; T-Cell Receptor; T-Lymphocyte; TCR Activation; Testing; Th2 Cells; Tissue Differentiation; Tissues; Transcript; Translating; Translations; Upper arm; Viral; Work; biological adaptation to stress; cell type; cytokine; eosinophil; immunopathology; in vitro Assay; in vivo; infectious disease model; insight; interest; lymph nodes; mRNA capping; neoplastic; novel; novel strategies; programs; response; transcription factor; upstream kinase

Effector immunity is mediated largely by cytokines, products of innate and differentiated adaptive T cells that orchestrate both host defense and immunopathology. Much research in immunology has focused on cells in lymphoid organs or during in vitro differentiation. Current interest has increasingly focusing on peripheral tissues, where effector cells carry out their functions. Using mice with knockin constructs that faithfully record cytokine transcripts, we find that naive helper T cells, when polarized to express specific cytokines, maintain IL-4 and IFN-gamma transcripts in an untranslated state in the cell, which we define as 'poised'. Reactivation leads to rapid translation of the previously transcribed message, facilitating rapid and flexible responses. This proposal seeks to define the extent to which priming of normal naive T cells establishes such a 'poised' effector state at the level of cytokine transcripts; to investigate mechanisms that contribute to maintaining the 'poised' state; and to use well-characterized murine parasite infection models - including Nippostrongylus brasiliensis and Leishmania major - to establish whether the relevant pathways exist in vivo. The proposal will use a variety of genetically modified mice together with molecular and biochemical assays to establish whether the process used by differentiating T cells is scaffolded onto more general cellular pathways for coordinating translation with fluctuating levels of protein secretion. Findings made in naive and differentiated helper T cells will be compared with effector cell populations that are resident in tissues, including NK cells, NK T cells and eosinophils. Such analysis may allow broad comparisons between different cell types that activate the IFN-gamma gene, the IL-4 gene, or both genes, potentially revealing core genetic programs linked intimately with effector function in the immune system.

效应免疫主要由细胞因子介导，细胞因子是先天和分化的适应性T细胞的产物