The roles of primitive T cells bearing Toll-like receptor in microbial infection.

细菌的Toll样受体(TLRs)不仅在吞噬细胞中表达，也在T细胞的某些亚群中表达。我们发现，携带Vγδ1的上皮δT细胞和携带Vα14的肝内NKT细胞表达TLRs，在细菌感染时肝损伤的保护和发病机制中发挥重要作用。结果如下：1.携带Y-γδ1的上皮性δT细胞在抵抗大肠杆菌感染的先天免疫中起关键作用，随后中性粒细胞大量涌入，随后巨噬细胞大量进入感染部位。我们发现，Vδ1^&lt；-/-&gt；小鼠在腹腔内接种大肠杆菌后，表现出腹膜巨噬细胞积聚受损，但中性粒细胞没有积聚，细菌清除延迟。来自野生型大肠杆菌感染小鼠的腹膜γδT细胞在体外对γδTCR的触发反应产生CCL_3/MIP-1a和CCL_5/RANTES，而在E.Coli感染的γδ小鼠的γδT细胞中没有明显的这种产生。CCl_3/MIP-1a…的中和体内多受一种特异性单抗明显抑制巨噬细胞感染后巨噬细胞在腹膜腔内的聚集，导致细菌在腹膜腔内的生长加剧。这些结果表明，在大肠杆菌感染过程中，Vδ1^+γδT细胞通过产生CC趋化因子，促进巨噬细胞向感染部位转运，在中性粒细胞和巨噬细胞之间架起一座桥梁。2肝内NKT细胞体内接种大肠杆菌后，肝内NK1.1^+T细胞表面Fas配体(Fas L)表达增强。在缺乏NK1.1+T细胞的Ja281^-lt；-/-&gt；小鼠和携带突变Fas L的GLD/GLD小鼠中，经血清谷丙转氨酶水平和组织学检查评估，感染大肠杆菌后的肝损伤明显减轻，表明NK T细胞至少部分地通过Fas/Fas L依赖的方式参与了大肠杆菌诱导的肝损伤。Ja281^&lt；-/-&gt；小鼠感染大肠杆菌后，脏器细菌数量和血清细胞因子水平与Ja281^&lt；+/+&gt；小鼠无明显差异。肝内优先表达TLR2的NK1.1^+T细胞在体外通过诱导其表面Fas-L的表达而对TLR2的配体合成脂蛋白产生反应。与大肠杆菌感染相似，脂蛋白和脂多糖可在NK1.1+T细胞上相加诱导Fas-L的表达，导致正常小鼠体内肝损伤，但对GLD/GLD小鼠无明显影响。结论：脂蛋白等细菌成分对NK T细胞表面Fas-L的诱导在大肠杆菌致小鼠肝损伤的发病机制中起重要作用。较少

Toll-like receptors (TLRs) for bacterial constitutes, are expressed not only by phagocytes but also by some subsets of T cells. We have found that epithelial γδ T cells bearing Vδ1 and intrahepatic NKT cells bearing Vα14 expressed TLRs and play an important role in protection and pathogenesis of liver injury during bacterial infection. as follows.1 Epithelial γδ T cells bearing Yδ1An influx of neutrophils followed a short time later by an influx of macrophages to the infected site plays a key role in innate immunity against Eschelichia coli infection. We found that Vδ1^<-/-> mice exhibited impaired accumulation of peritoneal macrophages but not neutrophils and delayed bacterial clearance after intraperitoneal inoculation with E.coli. Peritoneal γδ T cells from E.coli-infected wild-type mice produced CCL3/MIP-la and CCL5/RANTES in response to γδ TCR triggering in vitro, while such production was not evident in γδ T cells from E.coli-infected γδ1^<-/-> mice. Neutralization of CCL3/MIP-la … More by a specific monoclonal antibody in vivo significantly inhibited the accumulation of macrophages in the peritoneal cavity after E.coli infection, resulting in exacerbated bacterial growth in the peritoneal cavity. These results suggest that Vδ1^+γδ T cells bridge a gap between neutrophis and macrophages in innate immunity during E.coli infection mediated by production of CC chemokines, enhancing macrophage trafficking to the site of infection.2 Intrahepatic NKT cellsFas ligand (Fas L) expression was induced on intraheaptic NK1.1^+ T cells in vivo after an intraperitoneal inoculation of Escherichia coli. Liver injury after E.coli infection, as assessed by serum GPT level and histological examination, was significantly reduced in Ja281^<-/-> mice lacking NK1.1^+ T cells or in gld/gld mice bearing mutated Fas L, indicating that NK T cells at least partly contribute to E.coli-induced liver injury in a Fas/Fas L-dependent manner. Bacterial numbers in organs and cytokine levels in serum of Ja281^<-/-> mice did not differ from those of Ja281^<+/+> mice following E.coli infection. Intrahepatic NK1.1^+ T cells, which preferentially expressed TLR2mRNA, responded in vitro to synthetic lipoprotein, a ligand for TLR2, by inducing Fas L expression on their surface. In a manner analogous to E.coli infection, lipoprotein and LPS could additively induce Fas L expression on NK1.1^+ T cells, leading to liver injury in vivo in normal mice but not in gld/gld mice. In conclusion, it is suggested that induction of Fas L on NK T cells in response to bacterial components such as lipoproteins plays an important role in pathogenesis of E.coli-induced liver injury in mice. Less