Incidental appearance of suppressor T cells in the induction of immunological tolerance.

Adult C3H mice were rendered tolerant to human serum albumin (HSA) by weekly injections of the ultracentrifuged, soluble form of the antigen. Following these injections, generation of tolerance and of suppressor cells were examined to see if these phenomena were in any way correlated. On the weekly administration of 1.0 mg of soluble HSA (sHSA), suppressor cells were detected after 15 successive injections. At a dose of 2.5 mg of sHSA, suppressor cells were found earlier, i.e. after 3 and 6 injections but disappeared after 10 injections. Suppressor cells were also detected after increasing doses of sHSA, 0.1 mg, 0.5 mg and then 2.5 mg or 12.5 mg, given at intervals of 1 week. The kinetics of the appearance of suppressor cells was examined after these increasing doses of sHSA, and it was shown that they were found between 1 and 6 days after the last tolerogen injection. The suppressive activity of tolerized spleen cells was shown to be dependent on T cells and not due to carry-over of the tolerogen. From these experimental data, it is proposed that the generation of suppressor cells is not essential to tolerance induction by protein antigens, but that their appearance is concerned with regulation of the immune response which often accompanies tolerance induction.