Defect in rapidly clearing apoptotic cells leads to an accumulation of late apoptotic and secondary necrotic cells(dead cells),which results in inflammatory or autoimmune responses.Howerver,little is known about wheth...
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Defect in rapidly clearing apoptotic cells leads to an accumulation of late apoptotic and secondary necrotic cells(dead cells),which results in inflammatory or autoimmune responses.Howerver,little is known about whether and how macrophages(Mφs)cooperate with dendritic cells(DCs)in the processing and presentation of dead cell-associated Ags for expansion of T cells response in this process.By transferring high numbers of late apoptotic cells to mimic a failure ofapoptotic cell clearance in vivo,we demonstrated that Mφs and neutrophils were predominant phagocytes for uptake of dead cell-associated antigens(Ags)in the spleen.Moreover,both Mφs and DCs were required for augment of CD4+T cells response induced by dead cell-associated Ags.Importantly,after the phagocytosis,Mφs transferred cell-associated Ags to DCs,leading to Ag presentation to enhance T cells response although Mφs alone have poor presentation ability.Finally,we found that secrectory exosomes containing Ags from Mφs acted as transmitters between Mφs and DCs in a ceramide-dependent manner,since treatment with neutral sphingomyelinase(n SMase 2)inhibitor GW4869 resulted in a significant reduction of T cell proliferation in vitro and in vivo.Thus,these findings point to a novel pathway of cellular cross-talk between Mφs and DCs,which will be helpful to explain the mechanisms of immune response in autoimmune diseases characterized by increased rates of apoptosis.
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