PD-1 Controls Follicular T Helper Cell Positioning and Function

作者：Jingwen Shi, Shiyue Hou, Qian Fang, Xin Liu, Xiaolong Liu, Hai Qi · 发表于：Immunity · 年份：2018 · DOI：10.1016/j.immuni.2018.06.012 · 被引用次数：460 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、Cancer Immunotherapy and Biomarkers

Follicular T helper (Tfh) cells highly express the programmed cell death-1 (PD-1) molecule. Whereas inhibition of T cell receptor (TCR) signaling and CD28 co-stimulation is thought to be the primary mode of PD-1 functions, whether and how PD-1 regulates Tfh cell development and function is unclear. Here we showed that, when engaged by the ensemble of bystander B cells constitutively expressing PD-1 ligand 1 (PD-L1), PD-1 inhibited T cell recruitment into the follicle. This inhibition involved suppression of PI3K activities downstream of the follicle-guidance receptor CXCR5, was independent of co-signaling with the TCR, and necessitated ICOS signaling to overcome. PD-1 further restricted CXCR3 upregulation on Tfh cells, serving to concentrate these cells toward the germinal center territory, where PD-L1-PD-1 interactions between individual Tfh and B cells optimized B cell competition and affinity maturation. Therefore, operating in both costimulation-independent and -dependent manners, PD-1 controls tissue positioning and function of Tfh cells.