Reversibility of high dose unresponsiveness to concanavalin A in thymus lymphocytes.

Mouse thymus lymphocytes stimulated by Concanavalin A (Con A) displayed a typical dose curve with regard to induction of DNA synthesis. An optimal dose induced cellular proliferation, whereas both higher and lower Con A concentrations were inactive. When thymus lymphocytes were treated with Con A for 24 hours followed by removal of Con A by the addition of competing sugar and subsequently stimulated with Con A, the response was markedly enhanced as compared to cells continuously treated with Con A, but there was no change in the dose required for optimal induction of proliferation. The most enhancing effect was found after pretreatment with optimally stimulating doses of Con A. Cells pretreated with high doses of Con A, which were totally suppressive when present during the entire culture period, also exhibited a markedly enhanced response to an optimal dose of Con A. Similar results were obtained with cortisone-resistant thymocytes. The results show that the unresponsiveness caused by high concentrations of Con A requires the continuous presence of this substance. Furthermore, the unresponsive state was reversible and could be changed to a high response by removing the high concentration and subsequently challenging the cells with an optimally stimulating dose of Con A.