Division of Hematology-Oncology, Department of Medicine, and.
Abramson Family Cancer Research Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
J Clin Invest. 2020 Apr 1;130(4):1625-1628. doi: 10.1172/JCI136139.
Chronic graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic cell transplantation that resembles autoimmunity, with unclear pathogenesis and few effective therapeutic options. In this issue of the JCI, Dertschnig et al. used mouse models to investigate the basis of T cell autoreactivity following GVHD. Notably, GVHD caused irreversible damage to a population of tolerogenic stromal cells that display peripheral tissue-restricted antigens in lymph nodes, which impaired their capacity to purge and suppress autoreactive T cells. Together with damage to central tolerance mechanisms in the thymus, these findings outline a critical one-two punch injury that profoundly disrupts immune tolerance in this devastating disease.
慢性移植物抗宿主病（GVHD）是异基因造血细胞移植的主要并发症，类似于自身免疫，其发病机制尚不清楚，治疗选择也很少。在本期 JCI 中，Dertschnig 等人利用小鼠模型研究了 GVHD 后 T 细胞自身反应的基础。值得注意的是，GVHD 对一群具有免疫原性的基质细胞造成了不可逆转的损伤，这些细胞在淋巴结中表达外周组织受限的抗原，从而损害了它们清除和抑制自身反应性 T 细胞的能力。加上胸腺中中枢耐受机制的损伤，这些发现概述了一种严重破坏这种破坏性疾病中免疫耐受的关键一二拳损伤。
