Lymphocyte trajectories after liver transplantation: immune mechanisms, clinical associations, and research priorities
- 1Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University
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.
Related
- Nonlinear associations of the neutrophil-to-lymphocyte ratio and derived neutrophil-to-lymphocyte ratio with asthma–COPD overlap prevalence: a cross-sectional study
- Epigenetic Lymphocyte Subset Associations Across Allergic Phenotypes in a Predominantly Pediatric Cohort
- Physiological Basis of Skeletal Muscle Electrical Stimulation in Heart Failure with Reduced Ejection Fraction: Established Mechanisms, Extrapolated Mechanisms and Translational Priorities
- Postoperative Recovery Trajectories of C-Reactive Protein, Neutrophil-to-Lymphocyte Ratio, and CRP-to-Albumin Ratio After Open Irrigation and Debridement for Native Knee Septic Arthritis: A Descriptive Single-Center Cohort Study
- Associations of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios with amputation risk in patients with diabetic foot disease: a systematic review and meta-analysis
BibTeX
@article{gao2026lymphocyte,
title = {{Lymphocyte trajectories after liver transplantation: immune mechanisms, clinical associations, and research priorities}},
author = {Jiajun Gao and Zhaoyun Shi and Xuantong Jin and Zhiqi Jiao and Zhenyu Xu and Genhua Ye and Yuhui Wang and Fangliang Guo and Lianbo Yang and Zhenming Gao},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1982931},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1982931/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Lymphocyte trajectories after liver transplantation: immune mechanisms, clinical associations, and research priorities
AU - Jiajun Gao
AU - Zhaoyun Shi
AU - Xuantong Jin
AU - Zhiqi Jiao
AU - Zhenyu Xu
AU - Genhua Ye
AU - Yuhui Wang
AU - Fangliang Guo
AU - Lianbo Yang
AU - Zhenming Gao
PY - 2026
DA - 2026/10/19
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1982931
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1982931/full
AB - 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.
SN - 1664-3224
ER -