Opposite Effects of 5-Hydroxymethyluracil on Mitogenic Response of T Cells Stimulated through T-Cell Receptor or through T-Cell Receptor and CD28 Co-Receptor Molecule

Abstract

The effect of a synthetic analog of "minor" pyrimidine base 5-hydroxymethyluracil (0.01-10 μg/ml) on the mitogenic response of donor peripheral blood T cells was studied in vitro under conditions of lymphocyte stimulation through T-cell receptor (antiCD3 monoclonal antibodies) or through T-cell receptor and CD28 co-receptor molecule (antiCD3 and antiCD28 monoclonal antibodies). 5-hydroxymethyluracil suppressed the mitogenic response of T cells stimulated with antiCD3 antibodies, which was paralleled by an increase in the count of silent cells and decrease in the count of dividing lymphocytes, but not by stimulation of apoptosis of activated cells. Under conditions of integration of stimuli (lymphocyte stimulation with antiCD3 and antiCD28), 5-hydroxymethyluracil stimulated the mitogenic response, which was paralleled by suppression of activation apoptosis and increase in proliferative potential of cells.