title: Chronic ethanol exposure alters leukocyte subsets in repopulating spleens, but does not alter negative selection in thymuses of sublethally irradiated mice.
abstract: Results from previous in vitro experiments in this laboratory suggested that ethanol may affect selection processes in the thymus. To determine whether ethanol allows escape of potentially autoreactive T-cell clones from negative selection, we fed ethanol to sublethally irradiated, young, adult C57BR mice during the time of thymic and splenic repopulation as a new model of human third trimester fetal alcohol exposure. The mice received a whole-body, sublethal dose (6 Gy) of gamma irradiation 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 fed ad libitum (AD LIB). Average blood alcohol concentrations (90 to 440 mg/100 ml) were higher than those reported previously for neonatal mice exposed to ethanol through lactation. At 5 weeks after irradiation, the EDC mice had lower total thymocyte numbers (p < 0.05) and a higher proportion of CD4-CD8-thymocytes than either the PF or AD LIB mice (p < 0.05), which is consistent with findings using in utero models of ethanol exposure. Ethanol exposure also altered the proportion of leukocyte subsets in repopulating spleens. B cells were the most sensitive to the detrimental effects of ethanol and, as a percentage of total 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 mice normally delete by negative selection thymocytes bearing v beta 17 T-cell receptors. There was no discernible effect of ethanol exposure 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.
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, Auburn University, Alabama 36849-5519, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Livant
authors.forename: E G
authors.initials: EG
authors.lastname: Welles
authors.forename: S J
authors.initials: SJ
authors.lastname: Ewald
mesh_terms: D000437:Alcoholism / Q000276:immunology*; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D019891:Leukopoiesis / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects; D018655:Lymphocyte Count / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D011829:Radiation Dosage; D013154:Spleen / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects; D013950:Thymus Gland / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects
chemical_list: D000431:Ethanol