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Discovering new genes involved in protective T-cell responses through the generation of mice with targeted mutations

通过培育具有靶向突变的小鼠，发现参与保护性 T 细胞反应的新基因

基本信息

批准号：
10042745
负责人：
Luis J Sigal
金额：
$ 23.4万
依托单位：
THOMAS JEFFERSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10042745
关键词：
Adopted Animals Antibodies Antigens Antiviral Agents Antiviral Response Area Autoimmune Diseases Biology Bone Marrow CD3 Antigens CD44 gene CD8-Positive T-Lymphocytes CD8B1 gene Cells Cessation of life Chimera organism Communicable Diseases Cytotoxic T-Lymphocytes Development Disease Enzymes Exons Flow Cytometry Future Gene Deletion Generations Genes Genetic Transcription Gonadal structure Grant Granzyme Hematopoietic Human Immune Immune System Diseases Immune response Immune system Immunologic Deficiency Syndromes Immunology Inbred BALB C Mice Infection Infectious Ectromelia Knowledge Leukocytes Liver LoxP-flanked allele Maintenance Malignant Neoplasms Mammalian Oviducts Memory Methods Modeling Mouse Pox Virus Mouse Strains Mus Mutation PTPRC gene Peripheral Play Population Proteins RNA Reporter Resistance Role Site Spleen Splenocyte Stains T cell response T-Cell Activation T-Cell Development T-Lymphocyte Tamoxifen Thymus Gland Vaccines Viral Drug Resistance Viral load measurement Virus Diseases Work cancer therapy combat cost cytotoxic differential expression experience gene discovery gene function genome editing hepatic necrosis high risk immune resistance improved in vivo infectious disease treatment innovation insight mouse model novel nucleic acid delivery pathogen prevent resistant strain response transcriptome sequencing translational impact vaccine effectiveness

项目摘要

Abstract T-cells play major functions to combat infectious diseases and cancer, are critical for the effectiveness of vaccines, and may have negative effects in various types of immune disorders. While many of the genes involved in T-cell responses have been identified, it is likely that many remain unknown. The discovery of these genes and their specific roles during in vivo immune responses could provide major advances in our understanding of the immune system and for the improvement of vaccines and/or treatment of infectious diseases, cancer, and various immune disorders. Here we propose to generate mice with T-cell deletions of genes whose transcription is perturbed in specific T-cell populations during protective anti-viral T-cell responses. Our hypothesis is that some of these genes will play essential roles in immune responses to pathogens and possible in cancer and various immune dysfunctions. The mouse models developed through this grant will provide new valuable information about the role of still little-known genes in the modulation of the anti-viral immune response and resistance to viral infection and may be the basis of future novel discoveries encompassing not only immunology but other areas of mammalian biology.

摘要 T细胞在对抗传染病和癌症方面发挥着重要作用，疫苗的有效性，并可能对各种类型的免疫疾病产生负面影响。虽然许多参与T细胞反应的基因已经被鉴定出来，但很可能许多基因都与T细胞反应有关。仍然未知。这些基因的发现及其在体内免疫过程中的特殊作用，免疫反应可以为我们对免疫系统的理解提供重大进展，疫苗的改进和/或传染病、癌症和各种疾病的治疗免疫系统紊乱在这里，我们建议产生T细胞基因缺失的小鼠，在保护性抗病毒T细胞免疫过程中，应答我们的假设是，这些基因中的一些将在免疫系统中发挥重要作用。对病原体的反应，可能在癌症和各种免疫功能障碍中。鼠标通过这项赠款开发的模型将提供有关蒸馏器作用的新的有价值的信息。在调节抗病毒免疫反应和抵抗病毒感染方面，感染，可能是未来新发现的基础，不仅包括免疫学还有哺乳动物生物学的其他领域。