Negative co-stimulation constrains T cell differentiation by imposing boundaries on possible cell states Journal Article
| Authors: | Wei, S. C.; Sharma, R.; Anang, N. A. A. S.; Levine, J. H.; Zhao, Y.; Mancuso, J. J.; Setty, M.; Sharma, P.; Wang, J.; Pe'er, D.; Allison, J. P. |
| Article Title: | 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 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. © 2019 Elsevier Inc. Negative co-stimulation is a critical regulator of T cell activity. Wei et al. characterize T cells arising in CTLA-4- and PD-1-deficient mice via mass-cytometry and computational approaches. They show that these negative co-stimulatory molecules impose boundaries on T cell phenotypes during peripheral differentiation, suggesting that checkpoint blockade might work in part by altering the limits of T cell phenotypes. © 2019 Elsevier Inc. |
| Journal Title: | Immunity |
| Volume: | 50 |
| Issue: | 4 |
| ISSN: | 1074-7613 |
| Publisher: | Cell Press |
| Date Published: | 2019-04-16 |
| Start Page: | 1084 |
| End Page: | 1098.e10 |
| Language: | English |
| DOI: | 10.1016/j.immuni.2019.03.004 |
| PUBMED: | 30926234 |
| PROVIDER: | scopus |
| PMCID: | PMC6664799 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 May 2019 -- Source: Scopus |
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