Thiant Stéphanie, Moutuou Moutuaata M, Leboeuf Dominique, Guimond Martin
Maisonneuve-Rosemont Research Center, Montreal, Quebec, Canada; Department of Microbiology, Infectiology and Immunology, University of Montreal, Montreal, Quebec, Canada.
Department of Microbiology, Infectiology and Immunology, University of Montreal, Montreal, Quebec, Canada.
Cytokine. 2016 Jun;82:24-32. doi: 10.1016/j.cyto.2016.01.003. Epub 2016 Feb 1.
For numerous patients, allogeneic stem cell transplantation (SCT) is the only therapeutic option that could potentially cure their disease. Despite significant progress made in clinical management of allogeneic SCT, acute graft-versus-host disease (aGVHD) remains the second cause of death after disease recurrence. aGVHD is highly immunosuppressive and the adverse effect of allogeneic SCT on T cell regeneration is typically more important than the levels of immunosuppression normally seen after autologous SCT. In these patients, immune reconstitution often takes several years to occur and restoring immunocompetence after allogeneic SCT represents an important challenge, principally because clinical options are limited and current methods used to accelerate immune reconstitution are associated with increased GVHD. Interleukin-7 and IL-15 are both under clinical investigation and demonstrate the greatest potential on peripheral T cells regeneration in mice and humans. However, awareness has been raised about the use of IL-7 and IL-15 after allogeneic SCT with regards to potential adverse effects on aGVHD. In this review, we will discuss about recent progress made in lymphocyte regeneration, the critical role played by IL-7 and IL-15 in T cell homeostasis and how these cytokines could be used to improve immune reconstitution after allogeneic SCT.
对于众多患者而言，异基因干细胞移植（SCT）是唯一有可能治愈其疾病的治疗选择。尽管异基因SCT的临床管理取得了显著进展，但急性移植物抗宿主病（aGVHD）仍是疾病复发后第二大死亡原因。aGVHD具有高度免疫抑制性，异基因SCT对T细胞再生的不良影响通常比自体SCT后常见的免疫抑制水平更为重要。在这些患者中，免疫重建通常需要数年时间才能发生，而异基因SCT后恢复免疫能力是一项重要挑战，主要是因为临床选择有限，且目前用于加速免疫重建的方法与aGVHD增加有关。白细胞介素-7（IL-7）和IL-15均在临床研究中，并且在小鼠和人类外周T细胞再生方面显示出最大潜力。然而，关于异基因SCT后使用IL-7和IL-15对aGVHD的潜在不良影响，人们已经提高了认识。在本综述中，我们将讨论淋巴细胞再生方面的最新进展、IL-7和IL-15在T细胞稳态中所起的关键作用，以及这些细胞因子如何用于改善异基因SCT后的免疫重建。
