Acute graft versus host disease (aGVHD) is a rare, but severe complication of liver transplantation (LT). It is caused by the activation of donor immune cells in the graft against the host shortly after transplantation, but the contributing pathogenic factors remain unclear. Here we show that human T cell lymphotropic virus type I (HTLV-1) infection of donor T cells is highly associated with aGVHD following LT. The presence of HTLV-1 in peripheral blood and tissue samples from a discovery cohort of 7 aGVHD patients and 17 control patients is assessed with hybridization probes (TargetSeq), mass cytometry (CyTOF), and multiplex immunohistology (IMC). All 7 of our aGVHD patients display detectable HTLV-1 Tax signals by IMC. We identify donor-derived cells based on a Y chromosome-specific genetic marker, EIF1AY. Thus, we confirm the presence of CD4⁺Tax⁺EIF1AY⁺ T cells and Tax⁺CD68⁺EIF1AY⁺ antigen-presenting cells, indicating HTLV-1 infection of donor immune cells. In an independent cohort of 400 patients, we verify that HTLV-1 prevalence correlates with aGVHD incidence, while none of the control viruses shows significant associations. Our findings thus provide new insights into the aetio-pathology of liver-transplantation-associated aGVHD and raise the possibility of preventing aGVHD prior to transplantation.

急性移植物抗宿主病 (aGVHD) 是肝移植 (LT) 的一种罕见但严重的并发症。它是由移植物中的供体免疫细胞在移植后不久针对宿主的激活引起的，但促成的致病因素仍不清楚。在这里，我们显示供体 T 细胞的人类 T 细胞嗜淋巴病毒 I 型 (HTLV-1) 感染与 LT 后的 aGVHD 高度相关。使用杂交探针 (TargetSeq)、质谱细胞术 (CyTOF) 和多重免疫组织学 (IMC) 评估来自 7 名 aGVHD 患者和 17 名对照患者的发现队列的外周血和组织样本中 HTLV-1 的存在。我们的所有 7 名 aGVHD 患者都显示出可通过 IMC 检测到的 HTLV-1 Tax 信号。我们根据 Y 染色体特异性遗传标记 EIF1AY 识别供体来源的细胞。因此，我们确认 CD4 的存在⁺ Tax ⁺ EIF1AY ⁺ T 细胞和 Tax ⁺ CD68 ⁺ EIF1AY ⁺抗原呈递细胞，表明 HTLV-1 感染供体免疫细胞。在一个由 400 名患者组成的独立队列中，我们证实 HTLV-1 患病率与 aGVHD 发病率相关，而对照病毒均未显示出显着关联。因此，我们的研究结果为肝移植相关 aGVHD 的病因病理学提供了新的见解，并提高了在移植前预防 aGVHD 的可能性。