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Background: Adequate T-cell immune reconstitution (IR) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is pivotal for the recovery and optimal outcomes of pediatric HSCT recipients. A thorough assessment of global T-cell functionality is a crucial component in monitoring T-cell IR during the post-transplant period. The purpose of this study is to provide a novel tool and strategy for assessing and monitoring T-cell IR after pediatric allo-HSCT.
Methods: This study enrolled 126 pediatric patients receiving allo-HSCT at a single institution. A standardized whole blood interferon-gamma release assay (WB-IGRA) was introduced to evaluate global T-cell functionality in different periods after HSCT.
Results: The study revealed that T-cell functionality, assessed via the WB-IGRA assay, progressively enhanced over the post-transplant period, effectively distinguishing between patients with and without immunosuppression, thereby highlighting the assay's viability in assessment of T-cell IR in children after allo-HSCT. Further analysis stratified by age revealed a more significant enhancement in T-cell functionality among children >10 years old compared to those ≤10. Conversely, when evaluating immune cell subsets, increases in CD3, CD4, and CD8 subsets well reflected immune reconstructive progress in children ≤10 years old, whereas only increases in CD4 cell subsets exhibited statistical significance in older children. Additionally, all three T cell subset counts were significantly correlated with T-cell functionality in older children, whereas no such correlation was observed in younger ones.
Conclusions: This study demonstrated the potential application of the WB-IGRA approach in evaluating and monitoring T-cell IR in pediatric allo-HSCT recipients. Combining the assessment of T-cell immune functionality with cellular phenotypes could enhance the understanding of T-cell IR in HSCT children of different ages.
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http://dx.doi.org/10.21037/tp-2025-80 | DOI Listing |
Mem Inst Oswaldo Cruz
September 2025
Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório Interdisciplinar de Pesquisas Médicas, Rio de Janeiro, RJ, Brasil.
Background: Parasite antigens and plasma lipopolysaccharide (LPS) levels from luminal origin in visceral leishmaniasis (VL) patients are correlated with cellular activation and low CD4+T cell counts.
Objectives: Our aim was to verify whether Leishmania infantum infection damages the intestinal barrier and whether combination antimonial/antibiotic contributes to the reduction of LPS levels and immune activation.
Methods: Golden hamsters were grouped in: G1-uninfected; G2-infected with L.
Sci Adv
September 2025
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
(phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of in tumor cells increased expression of interferon-γ (IFN-γ)-regulated genes, including , , , and , even in the absence of IFN-γ stimulation in vitro.
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September 2025
Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University, Beijing, China.
Regulatory T cells are essential for immune homeostasis. While CD4 T cells are well characterized, CD8 T cells remain less understood and are primarily observed in pathological or experimental contexts. Here, we identify a naturally occurring CD8 regulatory precursor T cell at the steady state, defined by a CD8HLA-DRCD27 phenotype and a transcriptome resembling CD4 T cells.
View Article and Find Full Text PDFSci Transl Med
September 2025
Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
Hepatocyte apoptosis is a key feature of metabolic dysfunction-associated steatohepatitis (MASH), but the fate of apoptotic hepatocytes in MASH is poorly understood. Here, we explore the hypotheses that clearance of dead hepatocytes by liver macrophages (efferocytosis) is impaired in MASH because of low expression of the efferocytosis receptor T cell immunoglobulin and mucin domain containing 4 (TIM4; gene ) by MASH liver macrophages, which then drives liver fibrosis in MASH. We show that apoptotic hepatocytes accumulate in human and experimental MASH, using mice fed the fructose-palmitate-cholesterol (FPC) diet or the high-fat, choline-deficient amino acid-defined (HF-CDAA) diet.
View Article and Find Full Text PDFSci Transl Med
September 2025
Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, Shanghai 200032, P. R. China.
Triple-negative breast cancers (TNBCs) lack predictive biomarkers to guide immunotherapy, especially during early-stage disease. To address this issue, we used single-cell RNA sequencing, bulk transcriptomics, and pathology assays on samples from 171 patients with early-stage TNBC receiving chemotherapy with or without immunotherapy. Our investigation identified an enriched subset of interferon (IFN)-induced CD8 T cells in early TNBC samples, which predict immunotherapy nonresponsiveness.
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