Document Type
Article
Publication Date
4-2026
Identifier
DOI: 10.1097/HC9.0000000000000926; PMCID: PMC13038246
Abstract
BACKGROUND: Activated T-cell pediatric acute liver failure (TC-PALF) is the most common cause of non-acetaminophen PALF, with poor transplant-free survival. Livers in TC-PALF are infiltrated by effector cytotoxic T lymphocytes with markers of tissue-resident memory function (CD8 Trm) and an interferon gamma (IFNγ) transcriptional signature. The PALF-Immune Response Network (PALF-IRN) and the prospective TReatment for ImmUne-Mediated PathopHysiology (TRIUMPH) clinical trial (NCT04862221) aim to characterize the TC-PALF immune pathology and utility of T-cell directed therapy to improve transplant-free survival.
METHODS: TRIUMPH patients with TC-PALF were compared with healthy children and disease controls utilizing multiparameter flow cytometry and 3' single-cell RNA sequencing from peripheral blood mononuclear cells. TC-PALF patient serum was compared with healthy children and those with PALF from other causes, utilizing the Olink Inflammation I 384 protein assay.
RESULTS: Two distinct endotypes of TC-PALF were identified, which differed in flow cytometry CD8+ Perforin1 (Prf) expression and liver biopsy staining of Prf. TC-PALF patients with high CD8+ Prf (TC-PALF High Prf) had monocytosis, with a unique circulating CD8 IFNγ+ Trm-like population and IFNγ-responsive CD14/CD16 monocyte ligand-receptor interaction. TC-PALF patients with normal CD8+ Prf expression had hypergammaglobulinemia, an increase in class-switched B-cells, and a decrease in serum inflammatory proteins associated with myeloid activation.
CONCLUSIONS: TC-PALF high Prf patients have a unique circulating CD8+ IFNγ+ Trm-like population accompanied by monocyte proliferation and activation. Further understanding of the role of IFNγ in TC-PALF High Prf may provide a therapeutic target for this endotype to improve transplant-free survival.
Journal Title
Hepatol Commun
Volume
10
Issue
4
MeSH Keywords
Humans; Liver Failure, Acute; Interferon-gamma; Perforin; Child; Male; Female; CD8-Positive T-Lymphocytes; Child, Preschool; Infant; T-Lymphocytes, Cytotoxic; Adolescent; Lymphocyte Activation
PubMed ID
41921202
Keywords
CD8 T cells; aplastic anemia; immunology; liver failure; pediatrics
Recommended Citation
Diamond T, Chapin CA, Diorio CJ, et al. CD8 TRM-like T cells expressing perforin and IFN-γ define a pediatric activated T-cell acute liver failure endotype. Hepatol Commun. 2026;10(4):e0926. Published 2026 Mar 31. doi:10.1097/HC9.0000000000000926
Comments
Grants and funding
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Publisher's Link: https://journals.lww.com/hepcomm/fulltext/2026/04010/cd8_trm_like_t_cells_expressing_perforin_and_ifn__.11.aspx