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，发病机制不明，有效的治疗选择很少。在本期 JCI 中，Dertschnig 等人。使用小鼠模型研究 GVHD 后 T 细胞自身反应性的基础。值得注意的是，GVHD 对在淋巴结中显示外周组织限制性抗原的致耐受性基质细胞群造成不可逆转的损害，这削弱了它们清除和抑制自身反应性 T 细胞的能力。连同对胸腺中枢耐受机制的损害，这些发现概述了严重破坏这种破坏性疾病的免疫耐受的关键一两次冲击损伤。