The Effects Of Different Forms Of Programmed Cell Death On Cross-priming Of CD8~+ T Cells

Programmed cell death(PCD)is the death of cells in any form,mediated by intracellular signaling pathways.PCD plays an indispensable role in animal development and tissue homeostasis.Apoptosis,necroptosis and pyroptosis have received great attention in recent years.Mouse-model studies have revealed that PCD is implicated in the pathogenesis of many inflammatory diseases.Because cell death can also be inflicted merely by injury of the cells independent of activation of the PCD pathway,many natural PCD inducers are potent proinflammatory proteins.To directly study the effects of apoptosis,necroptosis and pyroptosis on immune system(innate and adaptive immune responses),we set up pure PCD models for apoptosis,necroptosis and pyroptosis by noninflammatory agents induced oligomerization of caspase-8,RIP3 and GSDMD.Compared to apoptosis,necroptosis and pyroptosis of cells released more damage-associated molecular patterns(DAMPs),and were more potent in eliciting innate immune cells and promoting DC maturation.Necroptotic cells,but not apoptotic cells or pyroptotic cells,could induce robust cross-presentation and cross-priming of CD8+ T cells.We showed that DCs more efficiently phagocytosed necroptotic cells than apoptotic and pyroptotic cells.Unlike apoptosis,necroptotic cells don't display a canonical 'eat me' signal of apoptosis.Our results reveal that local necroptotic cells can trigger and initiate a cascasding innate and adaptive immune responses in vivo.