| First Author | Wei SC | Year | 2019 |
| Journal | Immunity | Volume | 50 |
| Issue | 4 | Pages | 1084-1098.e10 |
| PubMed ID | 30926234 | Mgi Jnum | J:282637 |
| Mgi Id | MGI:6381255 | Doi | 10.1016/j.immuni.2019.03.004 |
| Citation | Wei SC, et al. (2019) Negative Co-stimulation Constrains T Cell Differentiation by Imposing Boundaries on Possible Cell States. Immunity 50(4):1084-1098.e10 |
| abstractText | 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 observed after anti-CTLA-4 and anti-PD-1 antibody blockade. These findings implicate negative co-stimulation as a key regulator and determinant of T cell differentiation and suggest that checkpoint blockade might work in part by altering the limits of T cell phenotypes. |
