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Effects of interleukin-18 on CD4⁺PD-1⁺ T cells may contribute to the pathogenesis of immune thrombocytopenia

YI Cen¹, ZHANG Cheng^2,3, LI Pei-Ning³, LI Wei-Ping², ZHOU Ying^2,*

¹Clinical Laboratory of Wuhan No. 1 Hospital, Wuhan 430022, China；²Department of Hematology, the Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China；³College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China

Abstract

The aim of this study was to investigate the regulatory effect and mechanism of interleukin-18 (IL-18) on the function of human peripheral blood CD4⁺ programmed death-1 (PD-1)⁺ T cells , and to explore whether the role of IL-18 was involved in the pathogenesis of immune thrombocytopenia (ITP). Peripheral anticoagulant samples were collected from ITP patients and healthy control subjects, and peripheral blood mononuclear cells (PBMCs) from healthy controls were isolated. CD4⁺PD-1⁺ T cells were isolated by immunomagnetic bead method and used to establish T and B cells co-culture system. ELISA was used to detect the contents of IgG and IgM in cell culture supernatant. Flow cytometry was used to detect cytokine and co-stimulatory molecule expression levels. MitoSOX mitochondrial superoxide indicator was used to detect mitochondrial reactive oxygen species (ROS) levels. The results showed that, under IL-18 stimulation, the expression levels of CD40L and inducible co-stimulator (ICOS) on the surface of healthy control CD4⁺PD-1⁺ T cells were significantly up-regulated, and the abilities of these T cells to assist B cells in producing antibodies were significantly enhanced. IL-18 stimulation increased the mitochondrial ROS levels in healthy control CD4⁺PD-1⁺ T cells, promoting the secretion of interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) by these T cells. This cytokine secretion promoting effect of IL-18 was inhibited by the ROS scavenger MitoQ. Compared to the healthy controls, the serum soluble PD-1 (sPD-1) level in the ITP patients was significantly increased. Under IL-18 stimulation, the sPD-1 level in the supernatant of healthy control CD4⁺ T cell culture was significantly increased. These results suggest that IL-18 may affect the function of CD4⁺PD-1⁺ T cells by regulating the production of mitochondrial ROS, and participate in their immune regulation through PD-1 pathway, thereby contributing to the pathogenesis of ITP.

Key words: immune thrombocytopenia; CD4⁺PD-1⁺ T cells; IL-18; mitochondrial reactive oxygen species

Received: 　　Accepted:

Corresponding author: 周莹　　E-mail:

DOI: 10.13294/j.aps.2025.0084

Citing This Article：

YI Cen, ZHANG Cheng, LI Pei-Ning, LI Wei-Ping, ZHOU Ying. Effects of interleukin-18 on CD4⁺PD-1⁺ T cells may contribute to the pathogenesis of immune thrombocytopenia. Acta Physiol Sin 2026; 78 (2): 433-442 (in Chinese with English abstract).