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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.

journal_name

Clin Exp Immunol

journal_title

Clinical and experimental immunology

authors

Hashimoto N,Shimoda S,Kawanaka H,Tsuneyama K,Uehara H,Akahoshi T,Kinjo N,Taketomi A,Shirabe K,Akashi K,Lleo A,Ansari AA,Gershwin ME,Maehara Y

doi

10.1111/j.1365-2249.2011.04393.x

subject

Has Abstract

pub_date

2011-08-01 00:00:00

pages

243-50

issue

eissn

0009-9104

issn

1365-2249

journal_volume

165

pub_type

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Modulation of CD4⁺ T cell responses following splenectomy in hepatitis C virus-related liver cirrhosis.