Modulation of T-Cell Adhesion Markers, and the CD45R and CD57 Antigens in Human Alcoholics

Direct and indirect evidence indicates that T cells are altered in alcoholics. The most commonly reported changes under direct examination have been consistent with an increased level of activation as reflected by shifts in the ratio of common leukocyte antigen isoforms expressed at the cell surface, by increases in the expression of class II antigen, or by alterations in the expression of various adhesion molecules. Functional evidence for T-cell abnormality includes loss of delayed hypersensitivity and a number of findings attributed to dysregulation of B cells by alcoholic T cells; these include the widely reported disturbances of immunoglobulin production in vivo and a range of abnormal responses when T and B cells are combined in vitro. Detailed flow cytometric examination of T cells from alcoholics with or without active liver disease reveals a significant loss of l -selectin CD8⁺ T cells, but not usually of CD4⁺ T cells. There is an inverse increase in the expression of CD11b on the CD8⁺ cells that have decreased L-selectin⁺ percentages. Both CD8⁺ and CD4⁺ T cells in alcoholics display a significant loss of the CD45RA isoform and a gain of cells exhibiting the CD45RO isoform. Other surface alterations include increased expression of CD57, a marker most commonly associated on T cells with conditions of chronic increased antigenic exposure. It is argued that these and other T-cell alterations in alcoholics are cytokine-driven in part and result in T-cell differentiation states that are functionally inappropriate. The results of these alterations may include reductions in normal lymphocyte traffic, an increase in cell-mediated cytotoxicity, and intermittent loss of normal suppressor functions for immunoglobulin production permitting increased autoantibody formation. Chronic excessive antigen exposure may contribute at other times to the development of abnormal regulatory suppression of the immune response.