Tempering dendritic cell activation

Immunotherapy Checkpoint blockade targeting cytotoxic T lymphocyte associated protein 4 (CTLA-4) and programed cell death 1 (PD-1) have changed the landscape of cancer therapeutics. However, much remains to be learned about the biology of these molecules. CTLA-4 expressed on T cells captures costimulatory molecules CD80 and CD86 from antigen-presenting cells by transendocytosis to inhibit CD28-mediated costimulation of T cell activation. Ovcinnikovs et al. report that regulatory T cells (Tregs) outperform conventional T cells in their ability to transendocytose CD80 and CD86 and that migratory dendritic cells are the main population targeted by Treg-expressed CTLA-4 in vivo. These findings elucidate why CTLA-4 expressed on Tregs is so central in maintaining immune homeostasis. Sci. Immunol. 4 , eaaw0902 (2019).