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Dependent1
Department of Bacteriology, University of Wisconsin, Madison, WI 53706
The role of variant surface glycoprotein (VSG)-specific Th cell
responses in determining resistance to the African trypanosomes was
examined by comparing Th cell responses in relatively resistant and
susceptible mice as well as in cytokine gene knockout mice infected
with Trypanosoma brucei rhodesiense. Resistant B10.BR
and C57BL/6 mice expressed Th1 cell cytokine responses to VSG
stimulation during infection, while susceptible C3H mice produced weak
or no Th1 cell cytokine responses. Neither resistant B10.BR and C57BL/6
mice nor susceptible C3H mice made detectable Th2 cell cytokine
responses to parasite Ag. To more closely examine the potential role of
IFN-
and other cytokines in host resistance, we determined the
resistance phenotypes and Th cell responses of IFN- and IL-4
knockout mice. Infected C57BL/6-IFN- knockout mice were as
susceptible as C57BL/6-scid mice and made an IL-2, but
not an IL-4, cytokine response to VSG, while C57BL/6-IL-4 knockout mice
were as resistant as the wild-type strain and exhibited both IL-2 and
IFN- cytokine responses. Passive transfer of spleen cells from
wild-type mice to IFN- knockout mice resulted in enhanced survival.
Both wild-type and IFN- knockout mice controlled parasitemia with
VSG-specific Ab responses, although parasitemias were higher in the
IFN- knockout mice. Overall, this study demonstrates for the first
time that relative resistance to African trypanosomes is associated
with a strong Th1 cell response to parasite Ags, that IFN-, but not
IL-4, is linked to host resistance, and that susceptible animals do not
make compensatory Th2 cell responses in the absence of Th1 cell
cytokine responses.
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