Gamma delta T cells act as rheostats to modulate early B cell response

Gamma delta T 细胞充当变阻器来调节早期 B 细胞反应

• 批准号: 8636277
• 负责人: Yueh-Hsiu Chien
• 金额: $ 28.28万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-20 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8636277
• 关键词: Adoptive Transfer; Affect; Affinity; Algae; Antibodies; Antibody Formation; Antigen-Presenting Cells; Antigens; B-Cell Activation; B-Lymphocytes; Bone Marrow; CCL3 gene; CCL4 gene; Cells; Chimera organism; Chronic; Collaborations; Communicable Diseases; Defense Mechanisms; Development; Environment; Failure; Frequencies; Future; Gene Expression Profile; Goals; Health; Human; Immune; Immunization; Immunoglobulin Class Switching; Infection; Interleukin-17; Intervention; Investigation; Life; Lyme Disease; Mus; Mutant Strains Mice; Nature; Observational Study; Phycoerythrin; Plasma Cells; Play; Population; Prevention; Process; Proteins; Research; Role; Series; Site; Source; Spleen; Staging; Structure of germinal center of lymph node; T-Cell Receptor; T-Lymphocyte; Testing; Time; Toxoplasmosis; Transgenic Mice; Vaccination; Vaccines; Vertebrates; Viral; Work; aluminum sulfate; base; chemokine; design; in vivo; insight; lymph nodes; migration; pathogen; protective effect; research study; response; vaccine development

DESCRIPTION (provided by applicant): Mounting an antibody response is a major immune defense mechanism used by all vertebrates. Similarly, nearly all vaccinations work by inducing an antibody response. However, not all antibody responses are protective. Sometimes, the antibodies that are generated are either too few in number, or too low in affinity - these kinds of responses are ineffective. Paradoxically, a strong antibody response may not protect the host either. Often, an exuberant early antibody response is associated with a failure to produce antibodies that are more effective in clearing the infection later on and the establishment of persistent infections. This phenomenon has been observed in bacterial (e.g. Lyme disease), viral (e.g. Herpes) and parasitic (e.g. Toxoplasma gondii) infections. Thus, an antibody response that is either too weak or too strong is not protective and may even do more harm than good; only the response, which is "just right", has the overall protective effect (the Goldilocks effect). The way to induce an antibody response has been well documented. However it is not at all clear how to regulate the strength of an antibody response in order to maximize protection. Because the lack understanding of the rules of augmenting antibody response, the rational design of effective vaccines remains unachievable and the prevention and treatment of chronic infections remain ineffective. This application, which is based on our recent findings suggesting γδ T cells may be uniquely suited to modulate the strength of early B cell response, seeks to establish the basis to test this hypothesis. Our ultimate goal is to identiy the principles that regulate the magnitude of antibody response in hopes of uncovering new points of intervention that can be used in vaccine development as well as to treat chronic infections.

描述（由申请人提供）：产生抗体反应是所有脊椎动物使用的主要免疫防御机制。同样，几乎所有的疫苗接种都是通过诱导抗体反应起作用的。然而，并非所有抗体反应都具有保护作用。有时，产生的抗体要么数量太少，要么亲和力太低，这些