Prolonged exposure to antigen induces specific unresponsiveness of mixed leukocyte culture-activated cells

One-way mixed leukocyte cultures, supplemented by the daily addition of small numbers of fresh stimulating cells between days 5 and 15 of incubation, failed to give a secondary proliferative or cell-mediated lympholytic response upon challenge with activating concentrations of the same stimulating. cells. However, these cultures could be fully activated by blastogenic factor (BF). The unresponsiveness induced was immunologically specific: when responding cells were primed simultaneously with stimulating cells from two donors and one stimulator was added daily, the cultures were unresponsive to challenge with cells of the stimulator which were added daily, but good secondary responses were elicited both by cells of the other stimulator used in priming and by BF. The induced unresponsiveness may be a consequence of specific inactivation of helper cells.