Tfh and B cells in HIV/SIV pathogenesis and vaccination

Tfh 和 B 细胞在 HIV/SIV 发病机制和疫苗接种中的作用

• 批准号: 9161747
• 负责人: Richard A Koup
• 金额: $ 127.39万
• 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/9161747
• 关键词: Antibody Response; B-Lymphocytes; Biology; CD4 Positive T Lymphocytes; Cell Communication; Cells; Characteristics; Chronic; Complex; Defect; Development; Goals; HIV; Helper-Inducer T-Lymphocyte; Human; Immunoglobulins; Infection; Molecular; Monkeys; Mus; Pathogenesis; Population; Predisposition; Process; Protocols documentation; Recruitment Activity; SIV; Signal Transduction; Structure of germinal center of lymph node; Vaccination; Virus; lymph nodes; neutralizing antibody; nonhuman primate; programs; spatiotemporal

Mouse, non-human primate (NHP) and human Tfh cells share phenotypic, functional and molecular programs which are regulated by local signals and spatiotemporal factors. Chronic HIV/SIV infection results in accumulation of Tfh, germinal center (GC) B cells and circulating virus-specific immunoglobulins in some subjects. However, most HIV/SIV infected subjects do not mount broadly neutralizing antibodies, pointing to functional defects in Tfh cells in chronic HIV/SIV infection. The susceptibility of particular CD4 T cells populations to HIV/SIV infection within lymph nodes notably impacts upon the dynamics of Tfh-GC B cell interactions. Some circulating CD4 T cells share certain characteristics with Tfh cells, however their direct origin from GC Tfh cells is not clear. There are many ways in which HIV and SIV influence the complex signals and mechanisms regulating the development of Tfh cells and their interactions with GC B cells. Understanding the biology of Tfh cells will be necessary to appropriately recruit these cells during vaccination with the goal of stimulating a more broad and potent neutralizing antibody response.

小鼠、非人灵长类(NHP)和人类Tfh细胞具有共同的表型、功能和分子程序，这些程序受局部信号和时空因素的调控。慢性HIV/SIV感染导致TfH、生发中心(GC)B细胞和循环中的病毒特异性免疫球蛋白在一些受试者中积聚。然而，大多数HIV/SIV感染者并没有安装广泛的中和抗体，这表明在慢性HIV/SIV感染中TFH细胞存在功能缺陷。淋巴结内特定的CD4T细胞群对HIV/SIV感染的易感性显著影响Tfh-GC B细胞相互作用的动态。某些循环中的CD4T细胞具有Tfh细胞的某些特征，但其直接来源尚不清楚。HIV和SIV通过多种途径影响调控TFH细胞发育的复杂信号和机制，以及它们与GC B细胞的相互作用。了解TFH细胞的生物学特性对于在疫苗接种期间适当地招募这些细胞，以刺激更广泛和更有效的中和抗体反应是必要的。