CHRONIC ETHANOL EXPOSURE ALTERS LEUKOCYTE SUBSETS IN REPOPULATING SPLEENS, BUT DOES NOT ALTER NEGATIVE SELECTION IN THYMUSES OF SUBLETHALLYIRRADIATED MICE

Results from previous in vitro experiments in this laboratory suggeste d that ethanol may affect selection processes in the thymus. To determ ine whether ethanol allows escape of potentially autoreactive T-cell c lones from negative selection, we fed ethanol to sublethally irradiate d, young, adult C57BR mice during the time of thymic and splenic repop ulation as a new model of human third trimester fetal alcohol exposure . The mice received a whole-body, sublethal dose (6 Gy) of gamma irrad iation at 5 to 6 weeks of age. Feeding of a liquid diet providing 25% of calories as ethanol (EDC) or an isocaloric control liquid diet was begun 3 days after irradiation and was continued for 5 weeks. Each EDC mouse had 2 weight-and age-matched controls, 1 pair-fed (PF), and 1 f ed ad libitum (AD LIB). Average blood alcohol concentrations (90 to 44 0 mg/100 ml) were higher than those reported previously for neonatal m ice exposed to ethanol through lactation. At 5 weeks after irradiation , the EDC mice had lower total thymocyte numbers (p < 0.05) and a high er proportion of CD4(-)CD8(-) thymocytes than either the PF or AD LIB mice (p < 0.05), which is consistent with findings using in utero mode ls of ethanol exposure. Ethanol exposure also altered the proportion o f leukocyte subsets in repopulating spleens, B cells were the most sen sitive to the detrimental effects of ethanol and, as a percentage of t otal nucleated cells in the spleen, B cells were decreased in the EDC group, compared with both the PF and AD LIB groups (p < 0.05). C57BR m ice normally delete by negative selection thymocytes bearing V beta 17 (+) T-cell receptors. There was no discernible effect of ethanol expos ure during thymic and splenic repopulation on the expression of V beta 17a on thymocytes and splenic T lymphocytes, indicating that ethanol does not affect negative selection.