The suppressive effect of 1, 25 (OH)₂D₃ on activated CD4 and CD8 cells

Abstract

It has been reported that the active form of vitamin D3, 1, 25 (OH)₂D₃(VD3), acts on activated T cells, especially on CD4 cells, and consequently suppresses DNA synthesis and the helper function. On the other hand, the effect of VD3 on CD8 cells is still unclear. We previously reported the suppressive effect of VD3 on both functions of CD4 and CD8 cells against immunoglobulin production in B cells. However, another report contracted our results on CD8 cells so we desired further information to define the effect of VD3 on CD8 cells compared to that on CD4 cells.
We assessed the DNA synthesis, interleukin 2 (IL 2) production and surface membrane antigen of CD8 cells as compared with those on CD4 cells. VD3 suppressed DNA synthesis of PWM-stimulated CD8 cells, as well as those of PWM-stimulated CD4 cells, in a dose-dependent manner. The DNA synthesis and IL 2 production of PHA-stimulated CD8 cells and CD4 cells were also suppressed by VD3 in a dose-dependent manner. These suppressive effect of VD3 were not observed on both subsets of cells unstimulated with mitogen. The expression of the IL 2 receptor on PHA-stimulated CD4 and CD8 cells was slightly suppressed at the middle or late phases of the culture. However, at the early phase of the culture, VD3 did not suppress the expression of the IL 2 receptor on both cells. In addition, VD3 failed to suppress DNA synthesis in CD4 and CD8 cells when cultured with IL 2, suggesting that VD3 intrinsically has no effect on IL 2-receptor expression and that the IL 2-receptor expressed in the culture with VD3 is functionally intact. The expression of the transferrin receptor on PHA-stimulated CD4 and CD8 cells decreased with the addition of VD3. Furthermore, this report states that VD3 suppressed the expression of Ia antigen on CD4 and CD8 cells, implying that, with reduced IL 2 production and DNA synthesis, this could be one possible cause of the deterioration of helper or suppressor activity in CD4 and CD8 cells by VD3.
Taken together, these results are reasonably in accord with our previous report, indicating that VD3 acts not specifically on CD4 cells, but on both CD4 and CD8 cells. Probably VD3 suppresses functions of CD4 and CD8 cells, via VD3 receptor, when activated and entered into a certain proliferative state. Thus our results suggest that, in the immune system in vivo, VD3 might play an important role in negative feedback regulation.