title: Decreased peripheral blood CD4+/CD25+ regulatory T cells in patients with alcoholic hepatitis.
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.
authors.affiliation: Cancer Research Center, (IBMCC; CSIC-USAL), IBSAL and Cytometry Service, University of Salamanca, Salamanca, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Almeida
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Polvorosa
authors.forename: Arturo
authors.initials: A
authors.lastname: Gonzalez-Quintela
authors.forename: Miguel
authors.initials: M
authors.lastname: Marcos
authors.forename: Isabel
authors.initials: I
authors.lastname: Pastor
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Hernandez Cerceño
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.forename: Francisco-Javier
authors.initials: FJ
authors.lastname: Laso
mesh_terms: D000209:Acute-Phase Proteins; D000328:Adult; D002352:Carrier Proteins / Q000097:blood; D016022:Case-Control Studies; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D006519:Hepatitis, Alcoholic / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D016207:Cytokines; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein
keywords: Alcoholic Hepatitis; CD4+ CD25hi CD127−/lo Tregs; Chronic Alcoholism; Inflammatory Cytokines