Reduced Alloreactive T-Cell Activation After Alcohol Intake is Due to Impaired Monocyte Accessory Cell Function and Correlates With Elevated IL-10, IL-13, and Decreased IFNgamma Levels

Citation data:

Alcoholism: Clinical and Experimental Research, ISSN: 0145-6008, Vol: 25, Issue: 12, Page: 1766-1772

Publication Year:
2001
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Repository URL:
https://escholarship.umassmed.edu/gastroenterology_pp/32; https://works.bepress.com/gyongyi_szabo/85
DOI:
10.1111/j.1530-0277.2001.tb02188.x
Author(s):
Szabo, Gyongyi; Mandrekar, Pranoti; Dolganiuc, Angela; Catalano, Donna; Kodys, Karen
Publisher(s):
Wiley-Blackwell
Tags:
Adult; Antigens, CD; Antigens, CD80; Antigens, CD86; Ethanol; Female; Flow Cytometry; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Humans; Interferon-gamma; Interleukin-10; Interleukin-13; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Male; Membrane Glycoproteins; Middle Aged; Monocytes; T-Lymphocytes; Gastroenterology; Immunology and Infectious Disease
article description
BACKGROUND: Immunosuppression associated with chronic alcohol use is characterized by reduced antigen-specific T-cell response and impaired delayed type hypersensitivity. Increasing evidence suggests in chronic alcohol consumption models that reduced antigen-specific T-cell proliferation is due to insufficient accessory cell function. Accessory cell function, a critical step in recognition of viral antigens, is reduced in chronic hepatitis C. The severity of hepatitis C is increased by alcohol consumption. Thus, we investigated the effects of alcohol consumption on accessory cell activity of monocytes in supporting alloreactive T-cell proliferation.METHODS: Alloreactive T-cell proliferation was evaluated in a one-way mixed lymphocyte reaction (MLR). Mononuclear cells were isolated by Ficoll density gradient and monocytes by adherence. Alcohol (0.8 g/kg body weight, an equivalent of approximately three drinks) was given to nonalcohol-consuming individuals and blood samples were collected before, 4 hr, or 18 hr after alcohol consumption. Alcohol in vitro was administered at concentrations of 25-100 mM.RESULTS: T-cell proliferation in MLR was significantly reduced in the presence of physiologically relevant concentrations of alcohol in vitro (25-100 mM ethanol) (p < 0.05). In vivo alcohol consumption also depressed proliferation in the MLR when stimulator cells were obtained 4 hr after alcohol consumption. MLR was not decreased, however, in the presence of alcohol-exposed responder cells and normal stimulator cells, suggesting that the accessory cell population and not T cells are affected by alcohol. Decreased accessory cell function was further evidenced by reduced superantigen-induced (SEB) but not mitogen-induced (PHA) T-cell proliferation in samples obtained 18 hr after alcohol intake (35% reduction). Reduced accessory cell function was not due to changes in surface expression of monocyte costimulatory molecules (HLA class I, HLA-DR, CD80, CD86, CD40). We found reduced IFNgamma, elevated IL-10, and unchanged IL-4 levels during T-cell proliferation in samples obtained 18 hr after alcohol consumption. Acute alcohol treatment resulted in increased IL-13 in the MLR.CONCLUSION: These data suggest that even on one occasion moderate alcohol intake can reduce allostimulatory T-cell activation via decreasing accessory cell function. Increased IL-10 and IL-13 plus the reduced IFNgamma production after acute alcohol use are likely to contribute to both the reduced T-cell proliferation and monocyte accessory cell function. These accessory cell mediated defects in T-cell activation may result in impaired antiviral and antitumor immunity after moderate acute alcohol use.