Department of Surgery, University of Melbourne, Heidelberg, Australia; Division of Surgery, Northern Health, Epping, Australia.
Department of Surgery, University of Melbourne, Heidelberg, Australia.
Transplant Rev (Orlando). 2022 Dec;36(4):100713. doi: 10.1016/j.trre.2022.100713. Epub 2022 Jul 9.
Prevention of T cell activation is one of the goals of successful organ and tissue transplantation. Blockade of T cell co-stimulation, particularly of the CD28:B7 interaction, has been shown to prolong graft survival. Inducible Co-Stimulator (ICOS) is the third member of the B7 family and here we review the literature on ICOS, its receptor (B7RP-1), and blockade of this pathway in transplant models. ICOS:B7RP-1 are a single receptor:ligand pair with a loss of function of either being implicated in some autoimmune diseases. ICOS has multiple functions, related to its constitutive expression on B cells and activated T cells. In in vitro transplant models, ICOS:B7RP-1 blockade has produced mixed results as to its ability to modulate lymphocyte proliferation. Several in vivo transplant models demonstrate varying degrees of success in prolonging graft survival. Timing and dose of treatment appear important, and combination with other immunosuppressive treatments may also be of benefit. As ICOS has multiple functions, it may be that the observed variable results are due to inadvertent inactivation of graft protective functions. If these barriers can be overcome, ICOS:B7RP-1 blockade could provide an important target for future immunosuppression regimens.
预防 T 细胞激活是成功进行器官和组织移植的目标之一。阻断 T 细胞共刺激，特别是 CD28:B7 相互作用，已被证明可以延长移植物的存活时间。诱导共刺激分子（ICOS）是 B7 家族的第三个成员，我们在这里回顾了关于 ICOS、其受体（B7RP-1）以及在移植模型中阻断该途径的文献。ICOS:B7RP-1 是一对单一的受体配体对，其功能丧失与某些自身免疫性疾病有关。ICOS 具有多种功能，与其在 B 细胞和活化 T 细胞上的组成性表达有关。在体外移植模型中，ICOS:B7RP-1 阻断在调节淋巴细胞增殖方面的效果不一。几种体内移植模型在延长移植物存活时间方面取得了不同程度的成功。治疗的时间和剂量似乎很重要，与其他免疫抑制治疗联合使用也可能有益。由于 ICOS 具有多种功能，观察到的可变结果可能是由于无意中使移植物保护功能失活。如果这些障碍能够克服，ICOS:B7RP-1 阻断可能为未来的免疫抑制方案提供一个重要的靶点。
