title: Modulation of CD4⁺ T cell responses following splenectomy in hepatitis C virus-related liver cirrhosis.
abstract: Dysfunction of T cells is a common feature in chronic persistent viral infections, including hepatitis C virus (HCV), and although hepatic and peripheral T cells have been studied extensively in chronic HCV hepatitis, the role of splenic T cell responses in such patients is poorly defined. This is an important issue, as thrombocytopenia is a complication of HCV-related liver cirrhosis (LC), due to splenic platelet sequestration and bone marrow suppression; splenectomy has been proposed to treat such patients. Herein, we studied peripheral blood mononuclear cells (PBMC) and splenic lymphoid subpopulations from a total of 22 patients, including 15 with HCV-related LC with marked thrombocytopenia treated with splenectomy, and seven controls. CD4(+) T cells from peripheral blood and spleen were isolated and phenotype and function evaluated. Splenic CD4(+) T cells in patients with LC expressed molecules associated with inhibitory signalling, including increased frequency of negative markers such as cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and programmed death 1 (PD-1) and decreased production of cytokines. Patients with LC manifest higher levels of splenic CD4(+) regulatory T cells and PD-L1- and PD-L2-expressing cells than controls. Blocking of PD-1/PD-1 ligand interaction reconstituted proliferative and cytokine responses of splenic mononuclear cells (SMC) from patients with LC. Splenectomy was followed by an increase in the ratio of interferon (IFN)-γ to interleukin (IL)-10 and a reduction of PD-1-expressing CD4(+) T cells in peripheral blood. Our data suggest that peripheral tolerance is promoted by the spleen in LC via the up-regulated expression of PD-1 ligands.
authors: Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
authors: N
authors: N
authors: Hashimoto
authors: S
authors: S
authors: Shimoda
authors: H
authors: H
authors: Kawanaka
authors: K
authors: K
authors: Tsuneyama
authors: H
authors: H
authors: Uehara
authors: T
authors: T
authors: Akahoshi
authors: N
authors: N
authors: Kinjo
authors: A
authors: A
authors: Taketomi
authors: K
authors: K
authors: Shirabe
authors: K
authors: K
authors: Akashi
authors: A
authors: A
authors: Lleo
authors: A A
authors: AA
authors: Ansari
authors: M E
authors: ME
authors: Gershwin
authors: Y
authors: Y
authors: Maehara
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