In vitro correction of the interleukin 2 defect of autoimmune mice.

The effect of concanavalin A (Con A) and/or phorbol myristate acetate (PMA) on interleukin 2 (IL 2) production and tritiated thymidine incorporation was measured in young (6 weeks) and old (16-24 weeks) autoimmune mice by pulsing 5 X 10(6) unfractionated spleen cells with 5 micrograms of Con A and/or 5 ng of PMA for variable periods of time. The apparent deficiency in Con A-stimulated IL 2 production manifested by mice prone to the development of autoimmune disease was repaired by the addition of PMA. PMA did not enhance interleukin 1 (IL 1) secretion in autoimmune MRL-lpr mice either alone or in combination with Con A. The addition of purified IL 1 to Con A-pulsed autoimmune cells did not increase IL 2 production. Freeze-thaw experiments suggested that PMA does not promote IL 2 synthesis. Con A-pulsed cells plus PMA-pulsed cells do not syngergize. These data indicate that autoimmune-prone mice are capable of producing IL 2 and of proliferating in response to Con A provided the comitogen PMA is present. It can be argued that the failure to produce IL 2 or to respond to proliferative signals is not fundamental to the development of the disease sustained by autoimmune-prone mice.