LEIF - A RECOMBINANT LEISHMANIA PROTEIN THAT INDUCES AN IL-12-MEDIATED TH1 CYTOKINE PROFILE

We have evaluated the ability of the Leishmania protein LeIF to influe nce the Th1/Th2 cytokine responses and the generation of LeIF-specific T cell clones in the absence of adjuvant, We characterized LeIF-speci fic T cell responses in Leishmania major-infected and uninfected BALB/ c mice. These mice develop a strong Th2 response during infection with L. major When lymph node cells from infected BALB/c mice were stimula ted in vitro with LeIF, only IFN-gamma land no detectable IL-4) was fo und in the culture supernatant. In addition, LeIF down-regulated Leish mania Ag-specific IL-4 production by lymph node cells from infected BA LB/c mice. Subsequently, Th responses were evaluated in naive BALB/c m ice following immunization with LeIF, T cell clones derived from mice immunized with LeIF preferentially secreted IFN-gamma. Finally, to und erstand the basis for the preferential Th1 cytokine bias observed with LeIF, the ability of LeIF to influence the early cytokine profile was evaluated in splenocytes of SCID mice. We found that LeIF stimulated fresh spleen cells from naive SCID mice to secrete IFN-gamma by IL-12/ IL-18-dependent mechanisms. The N-terminal half of the molecule (amino acid residues 1-226) maintained the ability to stimulate IFN-gamma fr om splenocytes of SCID mice. Finally, we also demonstrated that LeIF w as able to provide partial protection of BALB/c mice against L. major, Thus, our results suggest the potential of LeIF as a Th1-type adjuvan t and as a therapeutic and prophylactic vaccine Ag for leishmaniasis w hen used with other leishmanial Ags.