Graft-versus-host disease (GVHD) is a rare but fatal immune complication that can occur after liver transplantation (LT). GVHD following LT is thought to be induced by donor T cells transferred with the liver graft, 1 however, the clonal expansion dynamics of the graft-versus-host (GVH) T cells in patients with GVHD remain poorly understood. Several predictive factors have been explored to facilitate prevention, early diagnosis, and treatment, including recipient age >65 years, donor-recipient age divergence (>20 years), donorrecipient human leukocyte antigen (HLA) allele discrepancy, basiliximab induction, and hepatocellular carcinoma status. Although these factors have been used to estimate the risk of developing GVHD, 2,3 they are also common in non-GVHD patients. We evaluated patients to describe the kinetics of GVH T cell clonal expansion and its association with LT GVHD and explored potential risk factors. | C A S E REP ORTSClinical characteristics of four patients with GVHD (Pt62 and Pt124 who died of sepsis, Pt1 and Pt143 who were cured), 12 control patients without GVHD having Model End-Stage Liver Disease scores similar to those of patients with GVHD before LT
T cells are the common type of lymphocyte to mediate allograft rejection, remaining long-term allograft survival impeditive. However, the heterogeneity of T cells, in terms of differentiation and activation status, the effector function, and highly diverse T cell receptors (TCRs) have thus precluded us from tracking these T cells and thereby comprehending their fate in recipients due to the limitations of traditional detection approaches. Recently, with the widespread development of single-cell techniques, the identification and characterization of T cells have been performed at single-cell resolution, which has contributed to a deeper comprehension of T cell heterogeneity by relevant detections in a single cell – such as gene expression, DNA methylation, chromatin accessibility, surface proteins, and TCR. Although these approaches can provide valuable insights into an individual cell independently, a comprehensive understanding can be obtained when applied joint analysis. Multi-omics techniques have been implemented in characterizing T cells in health and disease, including transplantation. This review focuses on the thesis, challenges, and advances in these technologies and highlights their application to the study of alloreactive T cells to improve the understanding of T cell heterogeneity in solid organ transplantation.
Acute-on-chronic liver failure (ACLF) is a complex clinical syndrome, and patients often have high short-term mortality. It occurs with intense systemic inflammation, often accompanied by a proinflammatory event (such as infection or alcoholic hepatitis), and is closely related to single or multiple organ failure. Liver inflammation begins when innate immune cells (such as Kupffer cells (KCs)) are activated by binding of pathogen-associated molecular patterns (PAMPs) from pathogenic microorganisms or damage-associated molecular patterns (DAMPs) of host origin to their pattern recognition receptors (PRRs). Activated KCs can secrete inflammatory factors as well as chemokines and recruit bone marrow-derived cells such as neutrophils and monocytes to the liver to enhance the inflammatory process. Bacterial translocation may contribute to ACLF when there are no obvious precipitating events. Immunometabolism plays an important role in the process (including mitochondrial dysfunction, amino acid metabolism, and lipid metabolism). The late stage of ACLF is mainly characterized by immunosuppression. In this process, the dysfunction of monocyte and macrophage is reflected in the downregulation of HLA-DR and upregulation of MER tyrosine kinase (MERTK), which weakens the antigen presentation function and reduces the secretion of inflammatory cytokines. We also describe the specific function of bacterial translocation and the gut–liver axis in the process of ACLF. Finally, we also describe the transcriptomics in HBV-ACLF and the recent progress of single-cell RNA sequencing as well as its potential application in the study of ACLF in the future, in order to gain a deeper understanding of ACLF in terms of single-cell gene expression.
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