APPLICANT'S ABSTRACT: Excessive alcohol consumption represents a major human health threat. Both clinical and laboratory evidence suggests that alcohol alters normal host defense mechanisms making alcoholic patients more prone to a variety of infections. The immune system is major defense against infection and mounts both humoral (antibody) and cell-mediated responses to infectious organisms. Ethanol apparently has a two-fold effect on the immune system of alcoholic patients; it enhances humoral immunity and impairs cell-mediated immunity. Most immune responses are regulated by helper T (Th) or suppressor T (Ts) lymphocytes with effector cells. In the mouse, Th cells can be divided into two subsets based upon function Th1 cells help cell-mediated immune response and Th2 are responsible for most humoral immunity. Recent studies show that Th1 and Th2 are coregulatory, e.g., IFN-gamma (interferon-gamma) produced by Th1 down-regulates Th2. We hypothesize that ethanol enhances humoral immunity by the impairment of Ts which regulate humoral immunity and/or by adversely affecting Th1 cell function. Our preliminary studies concur with this interpretation. Impairment of Th1 function by alcohol would limit down-regulation of Th2 and enhance the humoral immune response. Here we propose to examine the effect of alcohol consumption, in a controlled manner, on immune responses in inbred strains of mice to synthetic copolymer antigens. We have previously shown that the poly(Glu50Tyr50)(GT) and poly(Glu60Ala30Tyr10)(GAT) antigens are powerful tools in eliciting the genetic control of the role of regulatory T cells in both cellular and humoral immune responses. We will use these antigens to immunize alcohol-preferring inbred strains of mice. We will define the conditions under which ethanol alters the immune response and determine which cells of the immune system are affected by ethanol consumption. Both humoral and cell-mediated immune functions will be assayed in order to monitor Th2 and Th1 activity, respectively. This study should help elucidate the underlying mechanism(s) of the effect of ethanol on the immune response.