HTLV-1 infection of donor-derived T cells might promote acute graft-versus-host disease following liver transplantation

Chuan Shen, Yiyang Li, Boqian Wang, Zhipeng Zong, Tianfei Lu, Nokuzola Maboyi, Yuxiao Deng, Yongbing Qian, Jianjun Zhang (), Xianting Ding () and Qiang Xia ()
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Chuan Shen: Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University
Yiyang Li: Shanghai Jiao Tong University
Boqian Wang: Shanghai Jiao Tong University
Zhipeng Zong: Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University
Tianfei Lu: Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University
Nokuzola Maboyi: Shanghai Jiao Tong University
Yuxiao Deng: Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University
Yongbing Qian: Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University
Jianjun Zhang: Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University
Xianting Ding: Shanghai Jiao Tong University
Qiang Xia: Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-35111-w

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