CTLA-4–mediated transendocytosis of costimulatory molecules primarily targets migratory dendritic cells

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Science Immunology  31 May 2019:
Vol. 4, Issue 35, eaaw0902
DOI: 10.1126/sciimmunol.aaw0902

Tempering dendritic cell activation

Although 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, much remains to be learned about the biology of these molecules. CTLA-4 that is expressed on T cells has been shown to capture costimulatory molecules CD80 and CD86 from antigen-presenting cells by transendocytosis to inhibit CD28-mediated costimulation of T cell activation. Here, Ovcinnikovs et al. report that 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. The study reveals a greater appreciation as to why CTLA-4 expressed on Tregs is so central in maintaining immune homeostasis.

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