Splenic CD4+ and CD8+ T-cells highly expressed PD-1 and Tim-3 in cirrhotic patients with HCV infection and portal hypertension

Author:

Huang Na12,Zhou Rui12,Chen Haiyan12,Zhang Shu12,Li Jun12,Wei Wei13,Sun Jin1,Ren Song12,Li Baohua12,Deng Hong4,Yang Jun15,Ji Fanpu1246ORCID,Li Zongfang126

Affiliation:

1. National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

2. Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

3. Department of Oncology Surgery, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

4. Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

5. Department of Pathology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

6. Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education of China, Xi’an, China

Abstract

Introduction: The spleen plays an important role in regulating the immune response to infectious pathogens. T-cells dysfunction and exhaustion have been reported in patients with hepatitis B/C virus (HBV/HCV) infection, which contributes to persistent virus infection. The aims of this study were to investigate spleen-related evidence of immunosuppression and immune tolerance in HCV cirrhotic patients with portal hypertension (PH). Methods: The expression of programmed cell death 1 (PD-1), T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) and its ligand PD-L1/2, and Galectin-9 in the spleens and livers of HCV cirrhotic patients ( n = 15) was analyzed using real-time PCR and immunohistochemistry. Flow cytometry was used to evaluate the expression of PD-1 and Tim-3 on splenic T-cells and the peripheral blood T-cells before and after splenectomy ( n = 8). Results: Spleens from patients with PH showed significantly increased mRNA levels of PD-L2, Tim-3, Galectin-9, CD80, and CD86, and decreased levels of CD28 compared to control spleens (spleens removed due to traumatic injury) (all p < 0.05). Additionally, protein expression of inhibitory signaling molecules was significantly increased in both the spleens and livers of cirrhotic patients compared with controls (all p < 0.05). Peripheral blood and splenic CD4+ and CD8+ T-cells also expressed higher protein levels of PD-1, Tim-3, and CTLA-4 in cirrhotic patients as compared with healthy controls (all p < 0.05). The proportion of PD-1+CD4+T lymphocytes (26.2% ± 7.12% vs. 21.0% ± 9.14%, p = 0.0293) and Tim-3+CD8+ T lymphocytes (9.4% ± 3.04% vs. 6.0% ± 2.24%, p = 0.0175) in peripheral blood decreased followed splenectomy. Conclusion: The CD4+ and CD8+ T-cells in spleen and peripheral blood highly expressed PD-1 and Tim-3 in HCV-infected and cirrhotic patients with portal hypertension. Highly expressed PD-1 and Tim-3 in peripheral blood T-lymphocytes can be partly reversed following splenectomy.

Funder

National Natural Science Foundation of Shaanxi Province

National Natural Science Foundation of China

Publisher

SAGE Publications

Subject

Pharmacology,Immunology,Immunology and Allergy

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. PD-1/PD-L1 axis in organ fibrosis;Frontiers in Immunology;2023-05-19

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