Activation/suppression of the immune response in vitro by antigen and dextran sulfate I. Analysis by limiting dilution methods

Spleen cells of normal mice which were stimulated with either T‐dependent or T‐ independent antigens and dextran sulfate (DxS) in microcultures at limiting dilution show at low cell densities an increased frequency of responding units (B cells) with both types of antigens. At higher cell densities, DxS induces a suppression of the immune response as assessed by a declining frequency of expressed B cells. When T cells were decreased in number, the stimulating effect of DxS on T‐independent responses remained unaltered while the suppressive effect (dependent on cell density) was eliminated. It is suggested that DxS lowers the threshold of activation for regulatory T cells, i.e. of cells which under standard in vitro conditions remain unactivated, and which in the presence of DxS become activated. We conclude that the regulatory cells are rare and that they are not present in most low cell density cultures. The net effect is a potent activation in dilute cultures and lack of response in dense cultures.