The role of antigen and IL-12 in sustaining Th1 memory cells in vivo: IL-12 is required to maintain memory/effector Th1 cells sufficient to mediate protection to an infectious parasite challenge

IL-12 plays a central role in both the induction and magnitude of a primary Th1 response. A critical question in designing vaccines for diseases requi ring Th1 immunity such as Mycobacterium tuberculosis and Leishmania major i s the requirements to sustain memory/effector Th1 cells in vivo. This repor t examines the role of IL-12 and antigen in sustaining Th1 responses suffic ient for protective immunity to L. major after vaccination with LACK protei n (LP) plus rIL-12 and LACK DNA. It shows that, after initial vaccination w ith LP plus rIL-12, supplemental boosting with either LP or rIL-12 is neces sary but not sufficient to fully sustain long-term Th1 immunity. Moreover, endogenous IL-12 is also shown to be required for the induction, maintenanc e, and effector phase of the Th1 response after LACK DNA vaccination. Final ly, IL-12 is required to sustain Th1 cells and control parasite growth in s usceptible and resistant strains of mice during primary and secondary infec tion. Taken together, these data show that IL-12 is essential to sustain a sufficient number of memory/effector Th1 cells generated in vivo to mediate long-term protection to an intracellular pathogen.