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.
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.


CONCLUSIONS
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.
Szabo
G
G
Division of Gastroenterology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605-2324, USA. gyongyi.szabo@umassmed.edu
Mandrekar
P
P
Dolganiuc
A
A
Catalano
D
D
Kodys
K
K
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood*; D018793:Interleukin-13 / Q000097:blood*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018793:Interleukin-13; D008562:Membrane Glycoproteins; D016753:Interleukin-10; D000431:Ethanol; D007371:Interferon-gamma