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Decreased Peripheral Blood CD 4 + / CD 25 + Regulatory T Cells in Patients with Alcoholic Hepatitis
Author(s) -
Almeida Julia,
Polvorosa Maria Angeles,
GonzalezQuintela Arturo,
Marcos Miguel,
Pastor Isabel,
Hernandez Cerceño Maria Luisa,
Orfao Alberto,
Laso FranciscoJavier
Publication year - 2013
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12095
Subject(s) - flow cytometry , immune system , immunology , monocyte , alcoholic liver disease , alcoholic hepatitis , microbiology and biotechnology , chemistry , medicine , biology , cirrhosis
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 ( T regs) have been reported in diseases associated with an immune activation status, but no studies have focused so far, in investigating the distribution of T regs in chronic alcoholism and its potential association with liver disease. Here, we analyzed for the first time the frequency of peripheral blood ( PB ) T regs and T reg subsets in AH and its relationship with the production of inflammatory cytokines by PB monocytes and dendritic cells ( DC s). 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 CD 4 + CD 25 hi CD 127 −/lo Tregs and their maturation subsets (naïve, central memory, and peripheral memory T regs) was analyzed by flow cytometry. Spontaneous and in vitro‐stimulated production of inflammatory cytokines by PB monocytes and DC s was analyzed by flow cytometry at the cytoplasmic level. Results Patients with AH showed decreased ( p < 0.05) numbers of PB CD 4 + CD 25 hi CD 127 −/lo Tregs at the expense of all maturation‐associated subsets, while AWLD and healthy subjects showed a similar ( p > 0.05) distribution of PB CD 4 + CD 25 hi CD 127 −/lo T regs. Interestingly, significantly increased amounts of spontaneously produced inflammatory cytokines were found among circulating monocyte‐derived DC s 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 CD 4 + CD 25 hi CD 127 −/lo T regs 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 DC s and monocytes, and could facilitate the development of liver disease.