| Dendritic cells(DC) are the most potent professional antigen-presenting cells with the unique ability to prime na?ve T cells. Mature DC present antigen to T cell and activat T cell, initiating the immune response. More attention has been attracted to investigate how to control the immune response. In addition to T and B cells, the terminal fate and its regulatory mechanisms of DC after accomplishing the antigen presenting has benn investigated. Ingulli et al exposed fluorescent dye-labled DC to antigen, then transferred them together with na?ve specific TCR transgenic T cells to mice. After 48 hours, DC labled with fluorescent dye could not be found in the lymph node. Experiments ex vivo showed that the apoptosis of DC could be detected in a short time after DC cocultured with antigen-spcific CD4+ T cells in the presence of antigen. All the data suggest that DC receive signals from activated T cell and come to apoptosis at the same time when DC activate T cells so that the immune response can be down-regulated efficiently. But in what way do DC go to apoptosis? To this question, the answers at the present mainly focus on two points: the Fas system and MHC class â…¡molecules. But no exact conclusions have been achieved. To further elucidate this question, we investigated the possible factors from activated T cells that induce DC apoptosis from the two aspects.Part â… The enhancement effect of Fas signal on the maturation of DC and antigen-presenting capability and related mechanismsActivation-induced cell death (AICD) is an essential mechanism involved in regulating immune response and preventing from over-activation. Members of TNF receptor superfamily including Fas are involved in the regulation of activation-induced cell death. But whether Fas induces DC apoptosis remains to be elucidated. So we treated DC with the agonist mAb to Fas, Jo-2 to observe the effect of Fas engagement on the phenotype and function of DC and investigated the related mechanisms.Our results demonstrate that DC, no matter immature or mature DC, are resistant to apoptosis induced through the Fas pathway though Fas is expressed on the membrane surface of DC. Interestingly, engagement of Jo-2 can induce the phenotypical maturation including the upregulation of the expression of MHC class â…¡molecules and the costimulatory molecules and functional activation including the secretion of IL-1(, the promotion of phagocytosis, the capability of the allostimulatory activity andantigen presentation. We examined the activation of Caspase 1, finding it can be activated 0.5 hour after the treatment of Jo-2. Both Pan-caspase inhibitor ZVAD-fmk and the caspase 1 inhibitor YVAD can inhibit the production of IL-1( and the phenotypical changes at the same time. It suggests that Jo-2 induces the secretion of IL-1(, which causes the phenotypical and functional changes of DC, by activating caspase 1. We also find that the inhibitor of ERK, PD98059, can inhibit the secretion of IL-1( and the phenotypical changes of DC induced by Jo-2, suggesting ERK plays a role in the production of IL-1( induced by Jo-2. The mRNA level of IL-1( in the cytoplasm was detected by semi-quantitative RT-PCR, demonstrating that Jo-2 cannot increase the gene expression of IL-1(. It seems that FasL expressed on the activated T cells interact with Fas on the surface of DC, resulting in the activation of ERK and caspase 1 and the quick secretion of IL-1(, which enhances the capability of DC to prime T cells proliferation, as a result, positively regulates the immune response. Furthermore, we detected the phosphorylation of I(B and the nuclear translocation of NF-(B. The inhibitor of NF-(B does not influence the secretion of IL-1( and the phenotypical changes of DC caused by Jo-2, suggesting the secretion of IL-1( is independent of the activation of NF-(B. However, inhibition of NF-(B activation makes DC sensitive to apoptosis induced through Fas pathway, as a result, the R123low cells increase after the treatment of Jo-2, suggesting Jo-2 engagement provides survival sign...
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