MECHANISM OF THE IMPAIRED T-CELL PROLIFERATION IN ADULT-RATS EXPOSED TO ALCOHOL IN-UTERO

Although attempts have been made to assess the effect of ethanol on th e immune responses in individuals with fetal alcohol syndrome, there i s no consensus as to the effect of ethanol on the immune system. Evide nce that fetal alcohol-exposed (FAE) humans and animals have diminishe d proliferative response of T-cells to mitogenic lectins is well estab lished. However, little is known about the mechanism of a toxic effect of ethanol on T-cell growth. Thus, a rat model was used to delineate the mode of ethanol action on T-cell proliferation. We found that the diminished T-cell proliferation in young adult FAE rats was due to a d ecreased responsiveness to interleukin 2 (IL2), but not to an impaired production of IL2 and expression of IL2 receptors (IL2R). Furthermore , the decreased proliferative response did not result from the presenc e of an excessive suppressor T-cell activity. Measurements of Ca+2(i ) and T-cell proliferation were concurrently performed in batches of c ells from the same animals. It was demonstrated that an increase in C a+2(i) induced by Concanavalin A (Con A) in T-cells from FAE rats was not impaired, although the T-cell proliferation induced by Con A was significantly diminished. The results of the IL2-binding study showed that the K-d values and the number of both high- and low-affinity IL2R binding sites on the T-cells of FAE rats were comparable to those of pair-, or chow-fed rats. Finally, the results of the kinetics and rate of the internalization of IL2 showed that (1) the amount of the inter nalized IL2 was significantly reduced in T-cells from FAE rats, and (2 ) the half-time (t(1/2)) for dissociation of IL2 from the receptors in the T-cells from FAE rats was also greater than that of the control r ats. These results taken together indicate that ethanol suppresses T-c ell proliferation by interfering with events following the IL2 - IL2R interaction.