Absence of regulatory T-cell control of TH1 and TH17 cells is responsible for the autoimmune-mediated pathology in chronic graft-versus-host disease
Absence of regulatory T-cell control of TH1 and TH17 cells is responsible for the autoimmune-mediated pathology in chronic graft-versus-host disease
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DOI：
10.1182/blood-2007-05-091074
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发表时间：
2007-11-15
期刊：
影响因子：
20.3
通讯作者：
Drobyski, William R.
中科院分区：
文献类型：
--
作者：
Chen, Xiao;Vodanovic-Jankovic, Sanja;Drobyski, William R.
移植物抗宿主病（GVHD）是异基因骨髓移植（BMT）后的主要并发症。由同种异体反应性供体T细胞介导的急性GVHD转变为慢性GVHD的过程，其特征在于自身免疫的显著特征，长期以来一直未得到解决。在这项研究中，我们证明了GVHD相关的自身免疫，并通过扩展，慢性GVHD是由于在急性GVHD过程中的CD4（+）CD25（+）Foxp3（+）调节性T细胞的进行性丢失。这导致具有T0和T（H）17细胞因子表型的供体来源的CD4（+）T细胞扩增，所述细胞因子表型释放促炎性细胞因子并引起自身免疫介导的病理损伤。这些T细胞在移植后早期就存在，表明导致慢性GVHD的病理生理事件在GVHD的急性期启动。我们的结论是，缺乏CD4（+）CD25（+）调节性T细胞与未调节的T（H）1和T（H）17细胞偶联导致自身免疫的发展，供体来源的TO和T（H）17细胞作为急性和慢性GVHD之间的联系。
Graft-versus-host disease (GVHD) remains the major complication after allogeneic bone marrow transplantation (BMT). The process whereby acute GVHD mediated by alloreactive donor T cells transitions into chronic GVHD, which is characterized by prominent features of auto-immunity, has long been unresolved. In this study, we demonstrate that GVHD-associated autoimmunity and, by extension, chronic GVHD is attributable to the progressive loss of CD4(+)CD25(+)Foxp3(+) regulatory T cells during the course of acute GVHD. This leads to the expansion of donor-derived CD4(+) T cells with TO and T(H)17 cytokine phenotypes that release proinflarnmatory cytokines and cause autolmmune-mediated pathological damage. These T cells are present early after transplantation, indicating that the pathophysiological events that lead to chronic GVHD are set in motion during the acute phase of GVHD. We conclude that the absence of CD4(+)CD25(+) regulatory T cells coupled with unregulated T(H)1 and T(H)17 cells leads to the development of autoimmunity and that donor-derived TO and T(H)17 cells serve as the nexus between acute and chronic GVHD.