SUSCEPTIBILITY AND RESISTANCE TO LEISHMANIA-AMAZONENSIS IN H-2(Q) SYNGENEIC HIGH AND LOW ANTIBODY RESPONDER MICE (BIOZZI MICE)

H-2 syngeneic H and L (Biozzi) mice provide a model to study Leishmani a infections in which polar resistant and susceptible phenotypes are i ndependent from H-2 differences. High-Ab-responder (H) and low-Ab-resp onder (L) mice syngeneic at the H-2 locus (H-2(q)) were, respectively, susceptible and highly resistant to Leishmania amazonensis infection. L-mice resistance was associated with high IFN-gamma and transient IL -4 production by lymph node (LN) cells, in contrast with sustained IL- 4 and decreasing IFN-gamma production by susceptible H mice. IL-12 pro duction could be detected only in LN from resistant mice. The cytokine production pattern was consistent with preferential progression to a Th1-type response in resistant L-mice, and to a Th2-type response in s usceptible Ii-mice. We also investigated whether this shift towards Th 1- or Th2-type cytokine responses was dependent upon H or L antigen pr esenting cells' (APC) intrinsic ability to preferentially stimulate ei ther T-cell subset. To this end, LN-derived T-cell lines were grown fr om 12-day infected mice, when both strains produced IFN-gamma and IL-4 . L-derived T-cell lines developed a Th2 cytokine pattern whereas H-de rived T-cell lines produced IFN-gamma, IL-4 and IL-10 whatever the APC origin (H or L) used for their derivation. This work constitutes the first characterization of cellular immune responses to the intracellul ar parasite, L. amazonensis in H-2 syngeneic mice, an infection model in which polar resistant and susceptible phenotypes are determined by non-MHC genes.