The apoptotic ligands TRAIL, TWEAK, and Fas ligand mediate monocyte death induced by autologous lupus T cells
The apoptotic ligands TRAIL, TWEAK, and Fas ligand mediate monocyte death induced by autologous lupus T cells
复制标题
DOI：
10.4049/jimmunol.169.10.6020
复制
发表时间：
2002-11-15
影响因子：
4.4
通讯作者：
Richardson, BC
中科院分区：
文献类型：
--
作者：
Kaplan, MJ;Lewis, EE;Richardson, BC
个体与系统性输入红斑显示单核细胞凋亡显著增加的证据。这一过程至少在一定程度上是由自身反应性T细胞亚群介导的，该亚群在没有银的情况下杀死自身单核细胞。我们研究了T细胞介导的凋亡通路。检测凋亡配体TRAIL、TNF-like weak inducer of apoptosis （TWEAK）和Fas配体在狼疮T细胞上的表达，并探讨这些分子在单核细胞凋亡反应中的作用。我们报道这些凋亡配体介导了自体单核细胞诱导的死亡。这种细胞毒性与这些分子在活化T细胞上的表达增加有关，而不是与这些配体诱导狼疮单核细胞凋亡的易感性增加有关。这些结果确定了狼疮患者单核细胞凋亡增加的新机制。我们认为这种机制可能为自身免疫反应提供潜在的抗原物质来源，并干扰正常的清除机制。
Individuals with systemic Inputs erythematosus show evidence of a significant increase in monocyte apoptosis. This process is mediated, at least in part, by an autoreactive T cell subset that kills autologous monocytes in the absence of nominal Ag. We have investigated the apoptotic pathways involved in this T cell-mediated process. Expression of the apoptotic ligands TRAIL, TNF-like weak inducer of apoptosis (TWEAK), and Fas ligand on lupus T cells was determined, and the role of these molecules in the monocyte apoptotic response was examined. We report that these apoptotic ligands mediate the autologous monocyte death induced. by Inputs T cells and that this cytotoxicity is associated with increased expression of these molecules on activated T cells, rather than with an increased susceptibility of lupus monocytes to apoptosis induced by these ligands. These results define novel mechanisms that contribute to increased monocyte apoptosis characterizing patients with lupus. We propose that this mechanism could provide a source of potentially antigenic material for the autoimmune response and interfere with - normal clearing mechanisms.