Negative Co-stimulation Constrains T Cell Differentiation by Imposing Boundaries on Possible Cell States.

ABSTRACT: Co-stimulation regulates T cell activation, but it remains unclear whether co-stimulatory pathways also control T cell differentiation. We used mass cytometry to profile T cells generated in the genetic absence of the negative co-stimulatory molecules CTLA-4 and PD-1. Our data indicate that negative co-stimulation constrains the possible cell states that peripheral T cells can acquire. CTLA-4 imposes major boundaries on CD4⁺ T cell phenotypes, whereas PD-1 subtly limits CD8⁺ T cell phenotypes. By computationally reconstructing T cell differentiation paths, we identified protein expression changes that underlied the abnormal phenotypic expansion and pinpointed when lineage choice events occurred during differentiation. Similar alterations in T cell phenotypes were obse

SUBMITTER: Wei SC 

PROVIDER: S-EPMC6664799 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature