ETHANOL INGESTION INHIBITS CELL-MEDIATED IMMUNE-RESPONSES OF UNPRIMEDT-CELL RECEPTOR TRANSGENIC MICE

This paper introduces a transgenic (Tg) mouse in which the majority of the CD4-bearing T cells have T-cell receptors that react with ovalbum in (OVA) as a model for ethanol research. Although these Tg animals we re bred onto the BALB/c genetic background, a strain generally conside red to be nonpreferring in ethanol consumption, we determined that BAL B/c mice would consume an ethanol-containing liquid diet, without sign ificant mortality, and assessed alteration of specific immune response s. BALB/c, C57BL6 (B6), or (BALB/c x C57BL/6)F1 hybrid (CB6F1) mice we re fed LED containing 35, 30, 25, or 20% ethanol-derived calories. Sig nificant mortality (>40%) was seen only in BALB/c and pronounced weigh t loss was seen in BALB/c, B6, CB6F1 mice when they were fed the diet containing the greatest ethanol concentration (LED35). Diets containin g lesser amounts of ethanol did not cause mortality. Liquid diets cont aining greater than or equal to 30% ethanol-derived calories significa ntly impaired the chicken gamma-globulin-specific delayed hypersensiti vity responses in BALB/c, B6, and CB6F/mice without significantly affe cting the humoral immune response to sheep red blood cells. We show Ba t immunization of the Tg mice is not required for the development of a vigorous ''delayed hypersensitivity'' response to OVA or the I-A(d)-r estricted peptide OVA(323-399) in mice fed standard solid lab chow or liquid control diet In marked contrast, OVA Tg mice fed ethanol show a profound inhibition of this immune response, indicating that ethanol- induced inhibition of cell-mediated immunity occurs independently of a ntigen priming.