T Cell Subsets in Graft Versus Host Disease and Graft Versus Tumor.
T Cell Subsets in Graft Versus Host Disease and Graft Versus Tumor.
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DOI：
10.3389/fimmu.2021.761448
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发表时间：
2021
影响因子：
7.3
通讯作者：
Paczesny S
中科院分区：
文献类型：
--
作者：
Jiang H;Fu D;Bidgoli A;Paczesny S
异基因造血细胞移植（allo-HCT）是治疗恶性血液病和其他血液疾病的重要手段。不幸的是，急性移植物抗宿主病（aGVHD）仍然是allo-HCT后发病率和死亡率的主要来源，这限制了其在更广泛的患者中的使用。慢性移植物抗宿主病（cGVHD）也仍然是allo-HCT的最常见的长期并发症，据报道在存活超过100天的患者中发生在30-70%。慢性GVHD也是恶性疾病HCT后2年以上发生的非复发死亡率（NRM）的主要原因。移植物抗肿瘤（GVT）是同种异体HCT治疗血液系统恶性肿瘤的总体有益作用的主要组成部分。更好地了解GVHD的发病机制对于寻找新的GVHD防治靶点具有重要意义。新出现的数据表明不同T细胞亚群的作用相反，例如，产生IFN-γ的CD 4+和CD 8 + T细胞（Th 1和Tc 1）、产生IL-4的T细胞（Th 2和Tc 2）、产生IL-17的T细胞（Th 17和Tc 17）、产生IL-9的T细胞（Th 9和Tc 9）、产生IL-22的T细胞（Th 22）、T滤泡辅助细胞（Tfh）、调节性T细胞（Treg）和组织驻留记忆T细胞（Trm）。本文首先综述了促进T细胞亚群分化的细胞因子信号及其在GVHD发病机制中的作用。接下来，我们广泛探索了GVHD/GVT动物模型和人类中T细胞亚群的临床前发现。最后，我们讨论了最近的研究结果T细胞亚群在临床GVHD和目前的策略，以调节T细胞分化的治疗和预防GVHD患者的作用。进一步探索和概述GVHD中T细胞分化的免疫生物学，这将为维持allo-HCT的成功提供更多的治疗选择。
Allogeneic hematopoietic cell transplantation (allo-HCT) is an essential therapeutic modality for patients with hematological malignancies and other blood disorders. Unfortunately, acute graft-versus-host disease (aGVHD) remains a major source of morbidity and mortality following allo-HCT, which limits its use in a broader spectrum of patients. Chronic graft-versus-host disease (cGVHD) also remains the most common long-term complication of allo-HCT, occurring in reportedly 30-70% of patients surviving more than 100 days. Chronic GVHD is also the leading cause of non-relapse mortality (NRM) occurring more than 2 years after HCT for malignant disease. Graft versus tumor (GVT) is a major component of the overall beneficial effects of allogeneic HCT in the treatment of hematological malignancies. Better understanding of GVHD pathogenesis is important to identify new therapeutic targets for GVHD prevention and therapy. Emerging data suggest opposing roles for different T cell subsets, e.g., IFN-γ producing CD4+ and CD8+ T cells (Th1 and Tc1), IL-4 producing T cells (Th2 and Tc2), IL-17 producing T cells (Th17 and Tc17), IL-9 producing T cells (Th9 and Tc9), IL-22 producing T cells (Th22), T follicular helper cells (Tfh), regulatory T-cells (Treg) and tissue resident memory T cells (Trm) in GVHD and GVT etiology. In this review, we first summarize the general description of the cytokine signals that promote the differentiation of T cell subsets and the roles of these T cell subsets in the pathogenesis of GVHD. Next, we extensively explore preclinical findings of T cell subsets in both GVHD/GVT animal models and humans. Finally, we address recent findings about the roles of T-cell subsets in clinical GVHD and current strategies to modulate T-cell differentiation for treating and preventing GVHD in patients. Further exploring and outlining the immune biology of T-cell differentiation in GVHD that will provide more therapeutic options for maintaining success of allo-HCT.
影响因子：
4.8
作者：
Meguro A;Ozaki K;Hatanaka K;Oh I;Sudo K;Ohmori T;Matsu H;Tatara R;Sato K;Sakata Y;Nakae S;Leonard WJ;Ozawa K
通讯作者：
Ozawa K
影响因子：
4.8
作者：
Meguro, A.;Ozaki, K.;Oh, I.;Hatanaka, K.;Matsu, H.;Tatara, R.;Sato, K.;Leonard, W. J.;Ozawa, K.
通讯作者：
Ozawa, K.