Dying cells actively regulate adaptive immune responses

Dying cells have an important role in the initiation of CD8⁺ T cell-mediated immunity. The cross-presentation of antigens derived from dying cells enables dendritic cells to present exogenous tissue-restricted or tumour-restricted proteins on MHC class I molecules. Importantly, this pathway has been implicated in multiple autoimmune diseases and accounts for the priming of tumour antigen-specific T cells. Recent data have revealed that in addition to antigen, dying cells provide inflammatory and immunogenic signals that determine the efficiency of CD8⁺ T cell cross-priming. The complexity of these signals has been evidenced by the multiple molecular pathways that result in cell death and that have now been shown to differentially influence antigen transfer and immunity. In this Review, we provide a detailed summary of both the passive and active signals that are generated by dying cells during their initiation of CD8⁺ T cell-mediated immunity. We propose that molecules generated alongside cell death pathways - inducible damage-associated molecular patterns (iDAMPs) - are upstream immunological cues that actively regulate adaptive immunity.