The combined effect of IL-4 and IL-10 suppresses the generation of, but does not change the polarity of, type-1 T cells in Histoplasma infection

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Abstract
Dominant type-1 cytokine production is induced in a murine model of systemic histoplasmosis. We used this model to investigate whether the presence of antagonistic cytokines during T cell priming changes the polarity of T cells in response to Histoplasma infection. Before infection with Histoplasma capsulatum, mice were injected twice with goat anti-mouse IgD antiserum (GαMδ), which induced expression of dominant type-2 cytokines. At days 7 and 14 after infection, the GαMδ-treated mice had suppressed IFN-γ response and a significantly greater fungal burden in their spleens and lungs. The number of IFN-γ-producing cells as well as the level of IFN-γ produced per cell was greatly reduced. Not only CD4+ T cells but also CD8+ T cells were affected. The number of Histoplasma-induced IFN-γ-producing cells was partially restored in GαMδ-treated IL-4−/− and IL-10−/− mice and completely restored in IL-4−/−IL-10−/− mice. Thus, the combined effect of IL-4 and IL-10 suppressed the generation of IFN-γ-producing cells. A longitudinal study demonstrated that as IL-4 and IL-10 decreased, the number of Histoplasma-induced IFN-γ-producing cells rapidly increased, and fungal clearance improved, demonstrating that the presence of IL-4 and IL-10 did not permanently change the polarity of T cells.

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