ORIGINAL RESEARCH article
Front. Immunol.
Sec. T Cell Biology
This article is part of the Research TopicCellular and Molecular Mechanisms of T Cell Dysfunction: Implications for therapy in Chronic InflammationView all 3 articles
Flow Cytometric Analysis of immune cell subsets in adult Hemophagocytic Lymphohistiocytosis
Provisionally accepted
- West China Hospital, Sichuan University, Chengdu, China
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Purpose Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome characterized by dysfunction of cytotoxic T-cells (CTLs) and natural killer (NK) cells. The status of these immune cells during persistent inflammation remains unclear. This study aims to investigate the immune cell subsets, exhaustion and activation status, and cytotoxic functions of CTLs and NK cells in adult HLH. Furthermore, the features of immune cells in EBV-HLH patients before and after treatment with programmed death-1 (PD-1) inhibitors were also analyzed. Methods We utilized flow cytometry to evaluate the immune cells features in 75 adult HLH patients. Results Our study observed the skewed immune cell subsets, along with substantial exhaustion and activation in adult HLH patients. The Significant decreases were noted in NK, NKT, Tregs, CD4+TCM, CD8+TEMRA, and CD56dimCD16+ NK cells, while increases were found in CD56brightCD16-and CD56dimCD16-NK subsets. Exhaustion markers (PD-1, TIGIT, and PD-L1) were elevated in CD8+ T cells and NK cells, and activation markers (CD69, HLA-DR, and CD163) were higher in monocytes. Impaired IFN-γ production and reduced degranulation function were also detected in CD8+ T cells and NK cells. In EBV-HLH patients treated with PD-1 inhibitors, we observed an increase in cytotoxic CD8+ T cells and CD56dimCD16+ NK cells, and a decrease in CD56brightCD16-NK cells. Conclusion These findings suggest the impairments in cytotoxic immune cells, along with widespread immune exhaustion and aberrant activation in adult HLH. The results also indicate potential differentiation defects in CD8+ T cells and NK cells. PD-1 inhibitor treatment may contribute to partial functional recovery and support viral clearance in EBV-HLH, which warrant further investigation.
Keywords: hemophagocytic lymphohistiocytosis, Immune cell subsets, Epstein-Barr virus, PD-1 inhibitor, Flow Cytometry
Received: 02 Aug 2025; Accepted: 10 Nov 2025.
Copyright: © 2025 Qin, Zhou, Liu, Dai, Tang, Zhong, Chen, Zhu and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ting Liu, liuting@scu.edu.cn
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