Mp. Chang et al., IMPAIRED CYTOSOLIC-FREE CALCIUM RESPONSE IN SPLENIC T-CELLS FROM MICEFED WITH ETHANOL-CONTAINING DIET, International journal of immunopharmacology, 15(6), 1993, pp. 647-656
Calcium-dependent signal transduction pathways of T-cell proliferation
have been extensively studied in the past years. However, little is k
nown about effects of ethanol on the calcium-dependent signal transduc
tion pathway in T-cell proliferation. Thus, a murine model was used to
determine effects of ethanol in vivo on T-cell proliferation and the
intracellular free calcium concentration [Ca2+]i in response to Concan
avalin A (Con A) and recombinant IL2 (rIL2) in T-cells. Splenic cells
from young C57BL/6 mice, that had been fed on 3 different diets (ethan
ol-, maltose substitute- and standard liquid-diet) for 7-8 weeks were
tested for their proliferative responses to Con A and rIL2. Concurrent
ly, measurement was also made of [Ca2+]i in the nylon-wool-enriched re
sting T-cells induced by Con A and in Con-A-activated blast T-cells in
duced by rIL2. Our results showed that [Ca2+]i increases were seen in
the splenic T-cells from three different groups of mice following Con
A, but not rIL2 stimulation. However, this increase was much smaller i
n the splenic T-cells from ethanol-fed mice as compared to mice on mal
tose- or standard-diet. Furthermore, we also demonstrated that the imp
aired [Ca2+]i increase was seen in the T-cells of the same ethanol-fed
mice having decreased the proliferative response to Con A. This reduc
ed proliferation did not result from the presence of excessive suppres
sor T-cell activity. Finally, we also demonstrated that both the numbe
r of IL2 binding sites/cell and the K(d) values of the low- and high-a
ffinity 1L2R on the T-cells from ethanol-fed mice were unaltered. Beca
use evidence indicates that (1) a normal level of [Ca2+]i increase is
a prerequisite for the production of IL2 by mitogen-stimulated T-cells
, and (2) T-cells from ethanol-fed mice have normal capacities to prod
uce IL2 that is the crucial growth factor Controlling T-cells to progr
ess through the cell cycle, these lines of evidence taken together wit
h the results of this study suggest that the impairment in [Ca2+]i inc
reases in T-cells froin ethanol-fed mice may not be the primary factor
contributing to the diminished T-cell proliferation in the same mice.