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Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104
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-ß 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-
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-ß 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- production. Immunohistochemical studies showed
that anti-TGF-ß treatment resulted in increased nitric oxide
production within parasitized lesions. Our results suggest that TGF-ß
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-ß, even the relatively low levels of IFN- observed in mice
with dominant Th2-type responses are sufficient to activate macrophages
to destroy amastigotes within parasitized lesions.
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