THE ROLE OF IL-12 IN THE MAINTENANCE OF AN ESTABLISHED TH1 IMMUNE-RESPONSE IN EXPERIMENTAL LEISHMANIASIS

IL-12 initiates the development of cell-mediated immunity by promoting the differentiation of naive T cells into the Th1 phenotype, and is e ssential in the development of a Th1 immune response to the intracellu lar protozoan parasite, Leishmania major: The present study investigat ed whether IL-12 is also required for the maintenance and effector fun ction of an established Th1 immune response in L. major-infected mice. While neutralization of IL-12 compromised the ability of a leishmania l antigen-reactive Th1 cell clone to produce IFN-gamma in vitro, lymph node cells taken from 2-week L. major-infected mice were able to secr ete IFN-gamma in an IL-12-independent manner. However, when a short-te rm T cell line was established in vitro from lymph node cells, the pro duction of IFN-gamma again became IL-12 dependent. These results sugge st that other factors may compensate for IL-12 in vivo in promoting IF N-gamma production during L, major infection. To directly assess if IL -12 was required in vivo for resistance to L. major, we studied the ef fect of IL-12 neutralization on both a primary and secondary L. major infection in C3H mice. L. major infection in C3H mice is characterized by the development of a small lesion that heals by 8 weeks, and these animals are resistant to reinfection. As previously reported, adminis tration of anti-IL-12 monoclonal antibody (mAb) during a primary infec tion led to severe disease. However, mice that had healed from a prima ry infection with L. major and were treated with anti-IL-12 mAb were a s resistant as control animals. These findings suggest that once Th1 c ells have developed, their effector function in vivo is independent of IL-12, and that this independence is not due to an intrinsic property of the T cell, but to the microenvironment created by the infection.