Detection in vivo 6 hours after immunization of a mediator with possible antisuppressor activity

Immunization of mice with foreign proteins or particulate antigen induces the formation of immunoglobulin (Ig)-antigen complexes which are strongly cytophilic for T cells and have been shown recently to markedly enhance the 7 S antibody response. In this report we demonstrate that pretreatment of the animals with cyclophosphamide or anti-I-J antiserum eliminates the difference in the antibody response between the mice injected with the complexes and the controls, in other words, the enhancement. Six hours after allogeneic stimulation the serum of mice contains also a cytophilic (for T cells) Ig which most likely represents, as in the case of the foreign antigens, complexes of Ig with alloantigens. The allogeneically induced 6-h serum (6HS) contains a factor which enhances the cytotoxic T lymphocyte(s) (CTL) response in vivo. As with the 7S antibody response, pretreatment of mice with cyclophosphamide, in doses known to eliminate suppressor cell expression, "masks" the CTL enhancement of the allogeneically induced 6HS. The same result was also observed with the anti-I-J antiserum. In conclusion, the 6-h complexes in cyclophosphamide- and anti-I-J-treated mice do not produce a 7 S antibody or CTL response above that produced by the control group (no complexes). Using heat-treated allogeneic tumor cells, known to induce suppressor cells in vivo, we have shown that for a low dose of tumor cells, the allogeneically induced 6HS did not block the induction of suppressor cells, but completely blocked their function. These results suggest that the enhancement of both humoral and cell-mediated immunity by the 6HS (complexes) is likely to be due to interference with normal suppressor cell function, that is, an antisuppressor mechanism.