In:
International Journal of Immunopathology and Pharmacology, SAGE Publications, Vol. 35 ( 2021-01), p. 205873842110610-
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.
Type of Medium:
Online Resource
ISSN:
2058-7384
,
2058-7384
DOI:
10.1177/20587384211061051
Language:
English
Publisher:
SAGE Publications
Publication Date:
2021
detail.hit.zdb_id:
2505963-4
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