Regulatory mechanism of delayed-type hypersensitivity in mice: II. Effect of suppressor cells on the development of memory cells for delayed-type hypersensitivity

Abstract

Experiments were made to investigate the effect of suppressor cells on the development of the memory activity in primed mice and the “short-term” memory cells in the spleen for delayed-type hypersensitivity (DTH). The memory activity, manifested by the development of accelerated DTH response upon challenge with alum-absorbed ovalbumin (OA), was induced in mice primed with 0.2 μg urea-denatured ovalbumin (UD-OA). The memory cells in the spleen, which could transfer the ability to accelerate the DTH response into recipient mice and were found for a short period of time, as described previously (11), were obtained from mice primed 7 days previously with 0.2 μg UD-OA. Antigen-specific suppressor cells which could inhibit the DTH response were obtained from spleen of mice primed 4 days previously with 500 μg UD-OA or with 5 mg OA. When the suppressor cells were transferred into mice at the time of either priming with 0.2 μg UD-OA or challenge with alum-absorbed OA, they inhibited the development of the memory activity in the primed mice. The suppressor cells also inhibited the generation of the splenic memory cells when transferred into the memory cell donors at the time of priming, or inhibited the ability of the memory cells to accelerate DTH response when cotransferred with the splenic memory cells into recipient mice at the time of challenge. As measured by DNA synthesis, cell proliferation in the spleen was induced in mice stimulated by priming with 0.2 μg UD-OA. The proliferation was depressed by transferring the suppressor cells, in parallel with the suppression of the memory activity. These results indicate that the suppression of the development of the memory activity in the primed mice is accompanied by the suppression of the splenic memory cell development, suggesting that the “short-term” memory cells in the spleen play an essential role in the development of the memory activity in the primed mice. They also suggest that the suppressor cells can inhibit not only the induction of the memory cells initiated by priming, but also the subsequent development of the memory cells reinitiated by challenge, and that they do so by their ability to inhibit cell proliferation.