Braidotti Stefania, Granzotto Marilena, Curci Debora, Faganel Kotnik Barbara, Maximova Natalia
Department of Pediatrics, Institute for Maternal and Child Health-IRCCS Burlo Garofolo, 34137 Trieste, Italy.
Azienda Sanitaria Universitaria Giuliano Isontina (ASU GI), 34125 Trieste, Italy.
Biomedicines. 2024 Aug 14;12(8):1853. doi: 10.3390/biomedicines12081853.
Optimized use of prophylactic or therapeutic donor lymphocyte infusions (DLI) is aimed at improving clinical outcomes in patients with malignant and non-malignant hematological diseases who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). Memory T-lymphocytes (CD45RA-/CD45RO+) play a crucial role in immune reconstitution post-HSCT. The infusion of memory T cells is proven to be safe and effective in improving outcomes due to the enhanced reconstitution of immunity and increased protection against viremia, without exacerbating graft-versus-host disease (GVHD) risks. Studies indicate their persistence and efficacy in combating viral pathogens, suggesting a viable therapeutic avenue for patients. Conversely, using virus-specific T cells for viremia control presents challenges, such as regulatory hurdles, cost, and production time compared to CD45RA-memory T lymphocytes. Additionally, the modulation of regulatory T cells (Tregs) for therapeutic use has become an important area of investigation in GVHD, playing a pivotal role in immune tolerance modulation, potentially mitigating GVHD and reducing pharmacological immunosuppression requirements. Finally, donor T cell-mediated graft-versus-leukemia immune responses hold promise in curbing relapse rates post-HSCT, providing a multifaceted approach to therapeutic intervention in high-risk disease scenarios. This comprehensive review underscores the multifaceted roles of T lymphocytes in HSCT outcomes and identifies avenues for further research and clinical application.
优化预防性或治疗性供体淋巴细胞输注（DLI）的使用旨在改善接受异基因造血干细胞移植（allo-HSCT）的恶性和非恶性血液病患者的临床结局。记忆T淋巴细胞（CD45RA-/CD45RO+）在HSCT后的免疫重建中起关键作用。输注记忆T细胞已被证明在改善结局方面是安全有效的，这是因为免疫重建增强以及对病毒血症的防护增加，同时不会增加移植物抗宿主病（GVHD）风险。研究表明它们在对抗病毒病原体方面具有持久性和有效性，这为患者提供了一条可行的治疗途径。相反，与CD45RA记忆T淋巴细胞相比，使用病毒特异性T细胞控制病毒血症存在挑战，如监管障碍、成本和生产时间。此外，调节性T细胞（Tregs）的治疗性调节已成为GVHD研究的一个重要领域，在免疫耐受调节中起关键作用，可能减轻GVHD并降低对药物免疫抑制的需求。最后，供体T细胞介导的移植物抗白血病免疫反应有望降低HSCT后的复发率，为高危疾病情况下的治疗干预提供多方面的方法。这篇综述强调了T淋巴细胞在HSCT结局中的多方面作用，并确定了进一步研究和临床应用的途径。
