THE INDUCTION OF A PROTECTIVE RESPONSE IN LEISHMANIA MAJOR-INFECTED BALB C MICE WITH ANTI-CD40 MAB/

A protective immune response to the intracellular parasite Leishmania major requires the development of a Th1 CD4(+) T cell phenotype. We de monstrate herein that BALB/c mice, which normally develop a susceptibl e Th2 response to L. major infection, are protected when co-injected w ith an agonistic anti-murine CD40 mAb. Anti-CD40 mAb-mediated protecti on in this system was found to be T cell dependent, since it was not o bserved in C57BL/6 x 129 mice that were rendered T cell deficient (TCR beta(-/-) x TCR delta(-/-)) and L. major susceptible. Anti-CD40 mAb s timulation of L. major-infected BALB/c mice was accompanied by increas ed IL-12 and IFN-gamma production in draining lymph nodes, analyzed ei ther by direct expression, or in an antigen-specific in vitro recall a ssay. The protective role of these cytokines was indicated by the find ing that anti-CD40 mAb-mediated protection of L. major-infected BALB/c mice could be reversed by co-treating the animals with neutralizing a nti-IL-12 and/or anti-IFN-gamma mAb. Collectively, these data suggest that BALB/c mice develop a protective Th1 CD4(+) T cell response to L. major infection when co-injected with anti-CD40 mAb, While the CD40-C D40L interaction has been previously shown to be vital in the control of murine Leishmaniasis, the current study establishes in vivo that an ti-CD40 mAb treatment alone is sufficient to protect BALB/c mice from L. major infection and raises the possibility of utilizing this approa ch for vaccination strategies.