Thymic peptides in immune reconstitution and clinical outcome after allogeneic hematopoietic cell transplantation

Hannah Kunstek , Janneke Kieviet , Caroline Lindemans , Coco de Koning ∗ , Stefan Nierkens ∗
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Abstract

Patients with hematologic malignancies or nonmalignant diseases may undergo allogeneic hematopoietic cell transplantation (HCT), which represents a potential curative treatment. However, they are still at risk of life-threatening complications, such as relapse, acute graft-versus-host disease, and opportunistic infections. These complications are more likely if T-cell reconstitution is delayed during the initial 3 to 4 months after HCT. Therefore, it is of clinical importance to advance early peripheral T-cell expansion. The thymus is the cradle of T-cell production, but it is extremely sensitive to conditioning drugs used in HCT. As a result, egress of T cells from the thymus is abrogated during the first 3 to 6 months after HCT. Instead, early T-cell reconstitution depends on peripheral expansion of engrafted donor T cells. However, besides its established function to produce T cells, the thymus also produces thymic peptides with hormone-like activity. These molecules play an essential part in the development and nature of immune responses and may have a role in modulating T-cell expansion and function after HCT. In this review, we investigate the role of thymic peptides in shaping the dynamics of immune reconstitution early after HCT. Furthermore, we summarize current reports on clinical application of thymic peptides post-HCT and discuss their potential use in improving patient outcomes.
胸腺肽在异基因造血细胞移植后免疫重建和临床结果中的作用
摘要恶性血液病或非恶性血液病患者可进行同种异体造血细胞移植(HCT),这是一种潜在的治疗方法。然而,他们仍然面临危及生命的并发症的风险,如复发、急性移植物抗宿主病和机会性感染。如果t细胞重建在HCT后最初的3到4个月内延迟,这些并发症更有可能发生。因此,促进早期外周t细胞扩增具有重要的临床意义。胸腺是t细胞产生的摇篮,但它对HCT中使用的调理药物极为敏感。因此,在HCT后的前3至6个月,胸腺的T细胞的输出被消除。相反,早期T细胞重建依赖于移植供体T细胞的外周扩增。然而,除了产生T细胞的既定功能外,胸腺还产生具有激素样活性的胸腺肽。这些分子在免疫反应的发展和性质中发挥重要作用,并可能在HCT后调节t细胞的扩增和功能中发挥作用。在这篇综述中,我们研究胸腺肽在HCT后早期形成免疫重建动力学中的作用。此外,我们总结了胸腺肽在hct后临床应用的最新报道,并讨论了它们在改善患者预后方面的潜在用途。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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