Wong Yik Chun, McCaughan Geoffrey W, Bowen David G, Bertolino Patrick
Liver Immunology Program, Centenary Institute and AW Morrow Gastroenterology and Liver Centre, University of Sydney and Royal Prince Alfred Hospital , Sydney, NSW, Australia.
Liver Cancer and Injury Group, Centenary Institute and AW Morrow Gastroenterology and Liver Centre, University of Sydney and Royal Prince Alfred Hospital , Sydney, NSW, Australia.
Clin Transl Immunology. 2016 Oct 14;5(10):e102. doi: 10.1038/cti.2016.53. eCollection 2016 Oct.
Both experimental and clinical studies have shown that the liver possesses unique tolerogenic properties. Liver allografts can be spontaneously accepted across complete major histocompatibility mismatch in some animal models. In addition, some liver transplant patients can be successfully withdrawn from immunosuppressive medications, developing 'operational tolerance'. Multiple mechanisms have been shown to be involved in inducing and maintaining alloimmune tolerance associated with liver transplantation. Here, we focus on CD8 T-cell tolerance in this setting. We first discuss how alloreactive cytotoxic T-cell responses are generated against allografts, before reviewing how the liver parenchyma, donor passenger leucocytes and the host immune system function together to attenuate alloreactive CD8 T-cell responses to promote the long-term survival of liver transplants.
实验研究和临床研究均表明,肝脏具有独特的致耐受性特性。在一些动物模型中,肝同种异体移植物能够在完全主要组织相容性不匹配的情况下被自发接受。此外,一些肝移植患者能够成功停用免疫抑制药物,形成“操作性耐受”。已证明多种机制参与诱导和维持与肝移植相关的同种异体免疫耐受。在此,我们聚焦于这种情况下的CD8 T细胞耐受。我们首先讨论针对同种异体移植物的同种反应性细胞毒性T细胞应答是如何产生的,然后再探讨肝实质、供体过客白细胞和宿主免疫系统如何共同发挥作用以减弱同种反应性CD8 T细胞应答,从而促进肝移植的长期存活。