Unknown

Dataset Information

0

Strength of PD-1 signaling differentially affects T-cell effector functions.


ABSTRACT: High surface expression of programmed death 1 (PD-1) is associated with T-cell exhaustion; however, the relationship between PD-1 expression and T-cell dysfunction has not been delineated. We developed a model to study PD-1 signaling in primary human T cells to study how PD-1 expression affected T-cell function. By determining the number of T-cell receptor/peptide-MHC complexes needed to initiate a Ca(2+) flux, we found that PD-1 ligation dramatically shifts the dose-response curve, making T cells much less sensitive to T-cell receptor-generated signals. Importantly, other T-cell functions were differentially sensitive to PD-1 expression. We observed that high levels of PD-1 expression were required to inhibit macrophage inflammatory protein 1 beta production, lower levels were required to block cytotoxicity and IFN-γ production, and very low levels of PD-1 expression could inhibit TNF-α and IL-2 production as well as T-cell expansion. These findings provide insight into the role of PD-1 expression in enforcing T-cell exhaustion and the therapeutic potential of PD-1 blockade.

SUBMITTER: Wei F 

PROVIDER: S-EPMC3703988 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC4546887 | biostudies-literature
2017-06-24 | GSE100411 | GEO
| S-EPMC3544114 | biostudies-literature
| S-EPMC5074090 | biostudies-other
| S-EPMC4508888 | biostudies-literature
| S-EPMC6445861 | biostudies-literature
| S-EPMC5973810 | biostudies-literature
| S-EPMC8605340 | biostudies-literature
| S-EPMC10886855 | biostudies-literature
| S-EPMC5638927 | biostudies-literature