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Decreased Peripheral Blood CD4+/CD25+ Regulatory T Cells in Patients with Alcoholic Hepatitis

Authors

  • Julia Almeida,

    1. Cancer Research Center , IBSAL and Cytometry Service , University of Salamanca, Salamanca, Spain
    2. Department of Medicine , University of Salamanca, Salamanca, Spain
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  • Maria Angeles Polvorosa,

    1. Alcoholism Unit, Department of Internal Medicine , University Hospital of Salamanca and IBSAL, Salamanca, Spain
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  • Arturo Gonzalez-Quintela,

    1. Department of Internal Medicine , University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
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  • Miguel Marcos,

    1. Department of Medicine , University of Salamanca, Salamanca, Spain
    2. Alcoholism Unit, Department of Internal Medicine , University Hospital of Salamanca and IBSAL, Salamanca, Spain
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  • Isabel Pastor,

    1. Department of Medicine , University of Salamanca, Salamanca, Spain
    2. Alcoholism Unit, Department of Internal Medicine , University Hospital of Salamanca and IBSAL, Salamanca, Spain
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  • Maria Luisa Hernandez Cerceño,

    1. Department of Clinical Biochemistry , University Hospital of Salamanca, Salamanca, Spain
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  • Alberto Orfao,

    1. Cancer Research Center , IBSAL and Cytometry Service , University of Salamanca, Salamanca, Spain
    2. Department of Medicine , University of Salamanca, Salamanca, Spain
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  • Francisco-Javier Laso

    Corresponding author
    1. Department of Medicine , University of Salamanca, Salamanca, Spain
    2. Alcoholism Unit, Department of Internal Medicine , University Hospital of Salamanca and IBSAL, Salamanca, Spain
    • Cancer Research Center , IBSAL and Cytometry Service , University of Salamanca, Salamanca, Spain
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  • JA and MAP have equally contributed to this work and these authors should be considered as first author.
  • AO and F-JL have equally contributed to this work and these authors should be considered as last author.

Reprint requests: Prof. Francisco-Javier Laso, MD, PhD, Unidad de Alcoholismo, Servicio de Medicina Interna, Hospital Universitario de Salamanca, 37007 Salamanca, Spain; Tel.: +34 923 29 13 06; Fax: +34 923 29 47 39; E-mail: laso@usal.es

Abstract

Background

Development of alcoholic hepatitis (AH) may be favored by the activation of the innate immune response. Recently, decreased numbers of circulating regulatory T cells (Tregs) have been reported in diseases associated with an immune activation status, but no studies have focused so far, in investigating the distribution of Tregs in chronic alcoholism and its potential association with liver disease. Here, we analyzed for the first time the frequency of peripheral blood (PB) Tregs and Treg subsets in AH and its relationship with the production of inflammatory cytokines by PB monocytes and dendritic cells (DCs).

Methods

PB samples from 25 male patients with AH were studied; in parallel, 15 male chronic alcoholic patients without liver disease (AWLD) and 17 male healthy donors were also studied, as controls. The distribution of CD4+CD25hiCD127−/lo Tregs and their maturation subsets (naïve, central memory, and peripheral memory Tregs) was analyzed by flow cytometry. Spontaneous and in vitro-stimulated production of inflammatory cytokines by PB monocytes and DCs was analyzed by flow cytometry at the cytoplasmic level.

Results

Patients with AH showed decreased (p < 0.05) numbers of PB CD4+CD25hiCD127−/lo Tregs at the expense of all maturation-associated subsets, while AWLD and healthy subjects showed a similar (p > 0.05) distribution of PB CD4+CD25hiCD127−/lo Tregs. Interestingly, significantly increased amounts of spontaneously produced inflammatory cytokines were found among circulating monocyte-derived DCs and monocytes from AH (and AWLD) patients in comparison with healthy donors. Conversely, the ability of these cell subsets to produce cytokines after in vitro stimulation was lower (p < 0.05) in AH versus the 2 control groups.

Conclusions

PB CD4+CD25hiCD127−/lo Tregs are significantly decreased in patients with AH when compared to both healthy and AWLD; this may contribute to explain the more pronounced activation of the innate immune response observed in AH, as reflected by an increased secretion of inflammatory cytokines by PB DCs and monocytes, and could facilitate the development of liver disease.

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