Mp. Chang et al., MECHANISM OF THE IMPAIRED T-CELL PROLIFERATION IN ADULT-RATS EXPOSED TO ALCOHOL IN-UTERO, International journal of immunopharmacology, 16(4), 1994, pp. 345-357
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.