Tfh and B cells in HIV/SIV pathogenesis and vaccination

小鼠、非人灵长类动物（NHP）和人Tfh细胞共享表型、功能和分子程序，这些程序由局部信号和时空因素调节。慢性HIV/SIV感染导致Tfh、生发中心（GC）B细胞和循环病毒特异性免疫球蛋白在一些受试者中积累。然而，大多数HIV/SIV感染的受试者不产生广泛中和抗体，这表明慢性HIV/SIV感染中Tfh细胞的功能缺陷。淋巴结内特定CD 4 T细胞群体对HIV/SIV感染的易感性显著影响Tfh-GC B细胞相互作用的动力学。一些循环CD 4 T细胞与Tfh细胞共享某些特征，然而它们来自GC Tfh细胞的直接来源尚不清楚。HIV和SIV以多种方式影响调节Tfh细胞发育及其与GC B细胞相互作用的复杂信号和机制。了解Tfh细胞的生物学对于在疫苗接种期间适当招募这些细胞是必要的，目的是刺激更广泛和更有效的中和抗体应答。

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.