Mechanism of tolerance to DNCB-contact sensitivity induced by immunosuppressive agents

Specific unresponsiveness to DNCB contact sensitivity has been induced in guinea pigs by a combined application of two immunosuppressive agents, cyclophosphamide and antithymocyte serum, to guinea pigs during the period of sensitization with DNCB. This tolerance was specific since the reactivity to an unrelated hapten (oxazolon) was not impaired by the previous immunosuppressive treatment. The unresponsiveness induced by immunosuppressive treatment has not been reversed by an additional treatment with the high dose of cyclophosphamide known to reverse hapten-induced tolerance, and has not been transferred by parabiosis from tolerant to normal partners. From these results it is concluded that specific unresponsiveness induced by immunosuppressive agents is not mediated by suppressor cells but is rather based on clonal deletion. The relative in unstability of this tolerance may be due to formation of new antigen-reactive cells from undeleted precursors.