| First Author | Shi J | Year | 2018 |
| Journal | Immunity | Volume | 49 |
| Issue | 2 | Pages | 264-274.e4 |
| PubMed ID | 30076099 | Mgi Jnum | J:299413 |
| Mgi Id | MGI:6500769 | Doi | 10.1016/j.immuni.2018.06.012 |
| Citation | Shi J, et al. (2018) PD-1 Controls Follicular T Helper Cell Positioning and Function. Immunity 49(2):264-274.e4 |
| abstractText | 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. |
