FINE T-CELL SUBSETS IN ALCOHOLICS AS DETERMINED BY THE EXPRESSION OF L-SELECTIN, LEUKOCYTE COMMON ANTIGEN, AND BETA-INTEGRIN

Alcoholics admitted to the hospital solely for detoxication have been studied by flow cytometry to evaluate changes in the surface markers of peripheral blood leukocytes. As we have shown previously, such patients have an elevated percentage of CD8(hi) lymphocytes that are HLA DR(+); wenow demonstrate that they also have striking alterations in the quantitative relationships of the fine T-cell subsets. Both CD4(+) and CD8(hi) lymphocytes have a sharply reduced percentage of the L-selectin(+) CD45RA(+) subset, increased percentages of the CD45RA(-) subsets, and several other fine subset alterations. The fine subset profile suggests, according to current correlations of phenotype and function, that both CD4(+) suppressor inducer and CD4 dependent CD8(+) suppressor effector cells are reduced, whereas other subsets, including CD8(+) CTL or their precursors, are increased in relative percentages. Some of the phenotypic changes are reversible over the several days following withdrawal. In other results, the percentage of CDBhi lymphocytes expressing CD11b (beta-integrin) is shown to be reciprocal with the percentage expressing L-selectin both in normals and alcoholics. However, the regression function of CD11b vs. L-selectin on CD8(hi) cells is different for the alcoholics than for the normals, indicating an abnormality in the regulation of the expression of these two adhesion markers. Taken together, this abnormality of adhesion molecules and the fine subset alterations previously described indicate widespread changes in the peripheral lymphocytes of currently drinking alcoholics. These changes suggest functional deficiencies that may include alterations of lymphocyte traffic and other adhesion-dependent functions, and a shift in the balance of regulatory interactions.