Deciphering new mechanisms on T-cell costimulation by human mast cells

It is well established that full activation of T cells to recognize a specific antigen requires additional signals. These secondary signals are generated by the interaction of costimulatory molecules expressed on APCs. Classical APCs include DCs, macrophages, Langerhans cells, and B cells. However, in recent years, several haematopoietic and nonhaematopoietic cells have been described to express MHC class II antigens and, in appropriate conditions, costimulatory molecules. In this issue, Suurmond et al. [Eur. J. Immunol. 2016. 46: 1132-1141] show, for the first time, that human mast cells not only express costimulatory molecules of the TNF-receptor and CD28 families, but can also costimulate T cells through a yet-to-be-defined CD28-independent interaction.