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 alc oholics. The most commonly reported changes under direct examination h ave 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 antig en, or by alterations in the expression of various adhesion molecules. Functional evidence for T-cell abnormality includes loss of delayed h ypersensitivity and a number of findings attributed to dysregulation o f B cells by alcoholic T cells; these include the widely reported dist urbances of immunoglobulin production in vivo and a range of abnormal responses when T and B cells are combined in vitro. Detailed flow cyto metric examination of T cells from alcoholics with or without active l iver 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-selecti n(+) percentages, Bath CD8(+) and CD4(+) T cells in alcoholics display a significant loss of the CD45RA isoform and a gain of cells exhibiti ng the CD45RO isoform. Other surface alterations include increased exp ression of CD57, a marker most commonly associated on T cells with con ditions of chronic increased antigenic exposure. It is argued that the se and other T-cell alterations in alcoholics are cytokine-driven in p art 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 cytotoxici ty, and intermittent loss of normal suppressor functions for immunoglo bulin production permitting increased autoantibody formation. Chronic excessive antigen exposure may contribute at other times to the develo pment of abnormal regulatory suppression of the immune response.