Chronic graft-versus-host disease in inflammatory mice and mechanism of PD-1 monoclonal anti-body exacerbating the disease
10.3760/cma.j.cn421203-20230830-00070
- VernacularTitle:PD-1单克隆抗体加重allo-HSCT小鼠炎性损伤和cGVHD的机制研究
- Author:
Xiaofan LI
1
;
Fang LI
;
Zhiqiang XIE
;
Min XU
;
Yanhua ZHENG
;
Chunxiao HE
;
Xintong LI
;
Xuemei WEN
;
Nainong LI
Author Information
1. 福建医科大学附属协和医院血液科福建省血液病研究所福建省血液病学重点实验室，福州 350000
- Keywords:
Hematopoietic stem cell transplantation;
Inflammation;
Graft versus host disease;
Regulatory T cell
- From:
Chinese Journal of Organ Transplantation
2024;45(2):96-103
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the mechanism of exacerbating chronic graft versus host disease (GVHD) in mice with inflammatory status and enhancing immune injury in mice with PD-1.Method:Bone marrow and spleen cells of DBA/2 mice were injected into BALB/C mice pretreated with chemotherapy regimen (Flu+Bu) for constructing a chronic GVHD model. The animals were assigned into two groups of zymosan (100M SPL+10M BM+Zymosan) and control (100M SPL+10M BM+ PBS). After transplantation, two groups of mice were observed for weight changes, survival status and chronic GVHD manifestations. Target organ tissues were harvested for pathological scoring. Flow cytometry was employed for detecting cell subpopulations and surface co-stimulatory molecules in target organs. PD-1 monoclonal antibody was injected into inflammatory murine model. Mice were observed and target organ cells were harvested for subsets and co-stimulatory factors.Result:In in vivo experiments, zymosan group showed more significant changes of chronic GVHD with higher mortality rate, faster weight loss and more severe symptoms of GVHD. At Week 2 post-transplantation, hematoxylin-eosin stain of target organ tissue was performed for pathology examination. Zymosan group showed more lymphocyte infiltration, more severe inflammation and more significant tissue injury with higher GVHD pathological score. The proportion of M2 in liver/lung of zymosan group was significantly lower than that of control group ( P<0.05) and no significant difference existed in the proportion of M1. In in vivo experiments, M1 ratio of splenic cell spiked markedly in zymosan group as compared to control group while M2 ratio declined greatly. The secretions of IL-4 and IL-10 dropped significantly while co-stimulatory molecules CD80 and CD86 rose obviously. Conclusion:The worsening graft-versus-host disease in inflammatory mice with anti-PD1 treatment is associated with a decline of Treg proportion.
