JA and MAP have equally contributed to this work and these authors should be considered as first author.
Decreased Peripheral Blood CD4+/CD25+ Regulatory T Cells in Patients with Alcoholic Hepatitis
Article first published online: 29 MAR 2013
Copyright © 2013 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 37, Issue 8, pages 1361–1369, August 2013
How to Cite
Almeida, J., Polvorosa, M. A., Gonzalez-Quintela, A., Marcos, M., Pastor, I., Hernandez Cerceño, M. L., Orfao, A. and Laso, F.-J. (2013), Decreased Peripheral Blood CD4+/CD25+ Regulatory T Cells in Patients with Alcoholic Hepatitis. Alcoholism: Clinical and Experimental Research, 37: 1361–1369. doi: 10.1111/acer.12095
AO and F-JL have equally contributed to this work and these authors should be considered as last author.
- Issue published online: 26 JUL 2013
- Article first published online: 29 MAR 2013
- Manuscript Accepted: 9 JAN 2013
- Manuscript Received: 15 MAY 2012
- Plan Nacional sobre Drogas. Grant Number: 2007/020
- Ministerio de Sanidad y Consumo
- Red de Trastornos Adictivos. Grant Number: RD06/0001/0004
- Chronic Alcoholism;
- Alcoholic Hepatitis;
- CD4+ CD25hi CD127−/lo Tregs;
- Inflammatory Cytokines
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).
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.
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.
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.