IMPAIRED CYTOSOLIC-FREE CALCIUM RESPONSE IN SPLENIC T-CELLS FROM MICEFED WITH ETHANOL-CONTAINING DIET

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.