Immune cell landscape in a human decedent receiving a pig liver xenograft.

Abstract

Recent advancements in genetically engineered pigs have spurred research into pig-to-human xenotransplantation, particularly involving heart, kidney and liver. Here we characterize immune cell populations cells in both peripheral blood and transplanted liver in a human decedent who received a pig liver xenograft and who was monitored over the course of 10 days. Using single-cell RNA sequencing and spatial RNA sequencing, we found that T cells were progressively activated in the peripheral blood, whereas γδT cells and exhausted T cells infiltrated the pig liver extensively, indicating impaired adaptive immunity. Additionally, we identified two distinct monocyte clusters that may influence the coagulation and immune response after xenotransplantation. First, at an early phase after transplantation, THBS1⁺ monocytes had the potential to regulate coagulation through interaction with platelets via the THBS1-CD36 signaling pathway. Second, at a later phase, C1QC⁺ monocytes infiltrated the pig liver, potentially promoting T cell exhaustion through induction of CD274 (PD-L1) expression. In summary, our study highlights how innate immune cells may affect thrombotic and immune pathways after liver xenotransplantation and should spur further research to clarify the roles of THBS1⁺ and C1QC⁺ monocytes.