T follicular helper (Tfh) CD4+ T cell, germinal center, and antibody response dysfunction in human recurrent tonsillitis

人复发性扁桃体炎中滤泡辅助性 T (Tfh) CD4 T 细胞、生发中心和抗体反应功能障碍

• 批准号: 10366647
• 负责人: Shane P Crotty
• 金额: $ 500.7万
• 依托单位: LA JOLLA INSTITUTE FOR IMMUNOLOGY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-11 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10366647
• 关键词: Antibody Response; Antibody-mediated protection; Antigens; Antiviral Agents; B-Lymphocytes; Bacteria; Bacterial Infections; Biology; Biopsy; Blood; CD4 Positive T Lymphocytes; Cells; Cellular biology; Characteristics; Child; Childhood; Complex; Data; Disease; Effector Cell; Exhibits; Fine needle aspiration biopsy; Functional disorder; Generations; Helper-Inducer T-Lymphocyte; Heterogeneity; Human; Human Herpesvirus 4; Humoral Immunities; Immune response; Immunity; Immunization; Individual; Infection; Interleukin-9; Intervention; Link; Lung; Lymphoid Tissue; MHC Class II Genes; Medical; Memory; Molecular; Newborn Infant; Pathologic; Pertussis; Pertussis Vaccine; Phenotype; Play; Process; Property; Provider; Recurrence; Regulatory T-Lymphocyte; Reporting; Role; Source; Streptococcus pyogenes; Structure of germinal center of lymph node; T cell response; Techniques; Teenagers; Testing; Tissues; Tonsil; Tonsillectomy; Tonsillitis; Transforming Growth Factor beta; Vaccinated; Vaccination; Vaccines; Virus; Virus Diseases; adaptive immune response; cohort; cost effective; cytokine; cytotoxic; imprint; in vivo; individual response; infancy; innovation; lymph nodes; memory CD4 T lymphocyte; novel; pathogen; polarized cell; response; single-cell RNA sequencing; transcription factor; vaccine development; vaccine response

PROJECT SUMMARY Overall Component Vaccines are one of the most cost effective and extraordinarily successful medical interventions. Most of those vaccines depend on CD4 T+ cells and their help to B cells. Our understanding of in vivo, specific human CD4+ T cell responses to pathogens remains hazy, due to the complexity of the biology, the rarity of the cells, relatively inaccessible tissue localization, and technical challenges of identifying specific CD4+ T cells. Therefore, our approach to this serious problem has been to develop multiple new techniques to study human CD4+ T cells over the past several years. While CD4+ T cell-dependent antibody responses have been the source of protection for most licensed vaccines (Project 1), there is a very good argument to be made that many of the diseases for which we do not have successful vaccines require adaptive immune responses beyond antibodies for protection (Projects 2 and 3). The three Projects proposed here vigorously pursue an understanding of the mechanisms regulating human anti-pathogen CD4+ T cells, linked by new experimental approaches.

项目摘要 总体组件 疫苗是最具成本效益和非常成功的医疗干预措施之一。大多数这些 疫苗依赖于CD4 T+细胞及其对B细胞的帮助。我们对体内特异性人CD4+ T细胞的理解 由于生物学的复杂性，细胞的稀有性， 难以接近的组织定位和识别特异性CD4+ T细胞的技术挑战。所以我们的 解决这一严重问题的方法是开发多种新技术来研究人类CD4+ T细胞 在过去的几年里。虽然CD4+ T细胞依赖性抗体反应是保护的来源， 对于大多数获得许可的疫苗（项目1），有一个很好的论点，即许多疾病， 我们还没有成功的疫苗，需要抗体以外的适应性免疫反应来保护 （项目2和3）。在此提出的三个项目积极寻求对这些机制的理解， 调节人类抗病原体CD4+ T细胞，通过新的实验方法连接。