CB6F1 mice display intermediate susceptibility to Leishmania major
infection compared with the highly susceptible BALB/c and resistant C57BL/6 parental strains. During early weeks of
infection, these mice develop dominant Th2 type responses to L. major, although they eventually exhibit a Th2 to Th1 switch and spontaneously resolve their
infections. In this study, we have examined the effects of either
IL-12 or anti-
TGF-beta therapy on the immune response and course of disease in chronically infected CB6F1 mice. Local treatment with
IL-12 inoculated into the parasitized lesion at 4 wk of
infection induced a marked increase in IFN-gamma production but did not result in a significant reduction in numbers of parasite or promote more rapid healing. However, local treatment with an Ab to
TGF-beta led to both a decrease in parasite numbers and more rapid healing, despite the fact that such treatment did not significantly alter the pattern of
IL-4 and IFN-gamma production. Immunohistochemical studies showed that anti-
TGF-beta treatment resulted in increased
nitric oxide production within parasitized lesions. Our results suggest that
TGF-beta may play an important regulatory role during chronic stages of a L. major
infection by suppressing macrophage production of
nitric oxide and that, in the absence of
TGF-beta, even the relatively low levels of IFN-gamma observed in mice with dominant Th2-type responses are sufficient to activate macrophages to destroy amastigotes within parasitized lesions.