Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, China.
State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, China.
Front Immunol. 2021 Nov 24;12:764786. doi: 10.3389/fimmu.2021.764786. eCollection 2021.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most effective and potentially curative treatment for a variety of hematologic malignancies. However, graft-versus-host disease (GVHD) is a major obstacle that limits wide application of allo-HSCT, despite the development of prophylactic strategies. Owing to experimental and clinical advances in the field, GVHD is characterized by disruption of the balance between effector and regulatory immune cells, resulting in higher inflammatory cytokine levels. A reduction in regulatory T cells (Tregs) has been associated with limiting recalibration of inflammatory overaction and maintaining immune tolerance. Moreover, accumulating evidence suggests that immunoregulation may be useful for preventing GVHD. As opposed to CD4 Tregs, the CD8 Tregs population, which constitutes an important proportion of all Tregs, efficiently attenuates GVHD while sparing graft-versus-leukemic (GVL) effects. CD8 Tregs may provide another form of cellular therapy for preventing GVHD and preserving GVL effects, and understanding the underlying mechanisms that different from those of CD4 Tregs is significant. In this review, we summarize preclinical experiments that have demonstrated the role of CD8 Tregs during GVHD and attempted to obtain optimized CD8 Tregs. Notably, although optimized CD8 Tregs have obvious advantages, more exploration is needed to determine how to apply them in the clinic.
异基因造血干细胞移植（allo-HSCT）仍然是治疗各种血液系统恶性肿瘤的最有效和潜在治愈方法。然而，移植物抗宿主病（GVHD）是限制 allo-HSCT 广泛应用的主要障碍，尽管已经制定了预防策略。由于该领域的实验和临床进展，GVHD 的特征是效应和调节性免疫细胞之间的平衡被打破，导致炎症细胞因子水平升高。调节性 T 细胞（Tregs）的减少与限制炎症过度反应的重新校准和维持免疫耐受有关。此外，越来越多的证据表明，免疫调节可能有助于预防 GVHD。与 CD4 Tregs 相反，CD8 Tregs 群体构成了所有 Tregs 的重要比例，有效地减轻了 GVHD，同时保留了移植物抗白血病（GVL）效应。CD8 Tregs 可能为预防 GVHD 和保留 GVL 效应提供另一种细胞治疗形式，了解其与 CD4 Tregs 不同的潜在机制意义重大。在这篇综述中，我们总结了表明 CD8 Tregs 在 GVHD 中的作用的临床前实验，并尝试获得优化的 CD8 Tregs。值得注意的是，尽管优化的 CD8 Tregs 具有明显的优势，但仍需要更多的探索来确定如何将其应用于临床。
