Regulating the immune system via IL-15 transpresentation

Transpresentation has emerged as an important mechanism mediating IL-15 responses in a subset of lymphocytes during the steady state. In transpresentation, cell surface IL-15, bound to IL-15Rα is delivered to opposing lymphocytes during a cell–cell interaction. The events most dependent on IL-15 include the development and homeostasis of memory CD8 T cells, Natural Killer cells, invariant Natural Killer T cells, and intraepithelial lymphocytes. As lymphocyte development and homeostasis involve multiple steps and mechanisms, IL-15 transpresentation can have diverse roles throughout. Moreover, distinct stages of lymphocyte differentiation require IL-15 transpresented by different cells, which include both hematopoietic and non-hematopoietic cell types. Herein, we will describe the points where IL-15 transpresentation impacts these processes, the specific cells thought to drive IL-15 responses, as well as their role in the course of development and homeostasis.

► Transpresentation is the mechanism mediating IL-15 responses during homeostasis.
► Other mechanisms can induce IL-15 responses but their relevance in vivo is unclear.
► Memory CD8 T cells depend on IL-15 transpresented by DCs and macrophages.
► Development of CD8ααIELs requires enterocytes transpresent IL-15.
► Hematopoietic and non-hematopoietic cells transpresent IL-15 to NK and INKT cells.