Autoreactive murine Th1 and Th2 cells kill syngeneic macrophages and induce autoantibodies

D10 cells, a cloned Th2 line, become autoreactive following treatment with DNA methylation inhibitors like 5-azacytidine (5-azaC), and induce anti-DNA antibodies if injected into unirradiated syngenic mice. The mechanism by w hich the autoreactive cells break tolerance is unknown. To further define e ffector functions required, we asked if 5-azaC-treated Th1 cells could also induce autoimmunity. AE7 cells, a cloned Th1 line, were treated with 5-aza C and shown to become autoreactive and induce anti-DNA antibodies in vivo. Comparison of effector mechanisms demonstrated that the two cell lines secr eted a distinct repertoire of cytokines, and that only killing of syngeneic Mo was common to both AE7 and D10 cells. This suggests that Mo killing may be an early step in the induction of anti-DNA antibodies, providing antige nic nucleosomes and decreasing clearance of apoptotic material. Secretion o f cytokines promoting B cell differentiation may play a role, but no one cy tokine is required.