Vanderheyde N, Aksoy E, Amraoui Z, Vandenabeele P, Goldman M, Willems F
Laboratory of Experimental Immunology, Université Libre de Bruxelles, 808 Route de Lennik, B-1070 Brussels, Belgium.
J Immunol. 2001 Oct 1;167(7):3565-9. doi: 10.4049/jimmunol.167.7.3565.
Monocyte-derived dendritic cells (DC) were found to be cytotoxic for several tumor cell lines including Jurkat cells, which were killed through a calcium-independent pathway. K562 cells were resistant, excluding a NK cell-like activity. DC-mediated apoptosis did not involve classical death receptors because it was not reversed by blocking TNF/TNFR, CD95/CD95 ligand, or TNF-related apoptosis-inducing ligand/TNF-related apoptosis-inducing ligand receptor interactions. Fas-associated death domain-deficient, but not caspase-8 deficient, Jurkat cells were killed by DC. Indeed, caspase-8 cleavage was demonstrated in Jurkat cells cocultured with DC, and the use of specific caspase inhibitors confirmed that apoptosis triggered by DC was caspase-8 dependent. Furthermore, the involvement of Bcl-2 family members in the control of DC-mediated apoptosis was demonstrated by Bid cleavage in Jurkat cells cocultured with DC and resistance of Jurkat cells overexpressing Bcl-2 to DC-mediated cytotoxicity. Overall, these data indicate that monocyte-derived DC exert a caspase-8-dependent, Fas associated death domain-independent tumoricidal activity, a finding that could be relevant to their therapeutic use in cancer.
单核细胞衍生的树突状细胞（DC）对包括Jurkat细胞在内的多种肿瘤细胞系具有细胞毒性，这些肿瘤细胞系通过一条不依赖钙的途径被杀死。K562细胞具有抗性，排除了自然杀伤（NK）细胞样活性。DC介导的细胞凋亡不涉及经典死亡受体，因为阻断肿瘤坏死因子（TNF）/肿瘤坏死因子受体（TNFR）、CD95/CD95配体或TNF相关凋亡诱导配体/TNF相关凋亡诱导配体受体相互作用并不能逆转这种凋亡。Fas相关死亡结构域缺陷但半胱天冬酶-8（caspase-8）不缺陷的Jurkat细胞会被DC杀死。实际上，在与DC共培养的Jurkat细胞中证实了caspase-8的裂解，并且使用特异性caspase抑制剂证实DC触发的细胞凋亡是caspase-8依赖性的。此外，在与DC共培养的Jurkat细胞中Bid的裂解以及过表达Bcl-2的Jurkat细胞对DC介导的细胞毒性具有抗性，证明了Bcl-2家族成员参与了对DC介导的细胞凋亡的调控。总体而言，这些数据表明单核细胞衍生的DC发挥了一种caspase-8依赖性、Fas相关死亡结构域非依赖性的杀肿瘤活性，这一发现可能与其在癌症治疗中的应用相关。
