Work

Lymphocyte trajectories after liver transplantation: immune mechanisms, clinical associations, and research priorities

Year: 2026

Type: review

Abstract: Liver transplantation (LT) is an established treatment for end-stage liver disease, yet rejection, infection, biliary injury, post-transplant lymphoproliferative disorder, and tumour recurrence continue to limit outcomes. Post-transplant immune states reflect alloantigen exposure, immunosuppression, microbial or viral stimulation, and inflammation within the graft. This Review examines longitudinal changes in CD8 + and CD4 + T cells, regulatory and follicular T-cell populations, B cells, natural killer cells, mucosal-associated invariant T cells, and γδ T cells after LT. The most direct evidence concerns acute cellular rejection, in which transient effector activation, T helper 1/interferon-γ responses, multicellular T-cell–B-cell signatures, and graft-local clonal programmes have been described. Early infection has been linked to inhibitory-receptor coexpression and impaired protective function, although treatment exposure, viral history, and phenotype definitions affect interpretation. An increase in circulating regulatory T cells alone does not establish operational tolerance; donor specificity, suppressive stability, and intrahepatic localisation are also required. Evidence relating lymphocyte subsets to biliary, vascular, metabolic, and oncological outcomes is less direct and often comes from experimental or non-transplant studies. Meaningful interpretation requires attention to sampling time, anatomical compartment, cellular function, and treatment exposure. Serial blood phenotyping may be combined with functional assays, soluble immune-mediator or protein signatures, graft histology, immune-receptor repertoires, and selected single-cell or spatial analyses. This approach defines research priorities, not a validated score or treatment algorithm. Clinical use will require standardised sampling, prespecified outcomes, externally validated thresholds, and prospective strategy trials that assess both benefit and harm.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1982931