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
Date Issued
2004
Date
2004
Author(s)
Peng, Jung-Kuei
DOI
en-US
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 (GaMd), which induced expression of dominant type-2 cytokines. At days 7 and 14 after infection, the GaMd-treated mice had suppressed IFN-g response and a significantly greater fungal burden in their spleens and lungs. The number of IFN-g-producing cells as well as the level of IFN-g produced per cell was greatly reduced. Not only CD4+ T cells but also CD8+ T cells were affected. Reduction of IFN-g-producing T cells is not a result in T cell expansion, T cell death, or intrinsic defect in TCR signaling. There was no difference in the numbers of CD4 and CD8 T cells in infected mice with or without GaMd treatment. The number of Histoplasma-induced IFN-g-producing cells was partially restored in GaMd-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-g-producing cells. A longitudinal study demonstrated that as IL-4 and IL-10 decreased, the number of Histoplasma-induced IFN-g-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.
Subjects
組織胞漿菌炎
第一型第二型免疫反應
干擾素
Histoplasmosis
Type-1 and type-2 immune response
interferon
Type
other
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