STAT6 signalling is important in CD8+ T-cell activation and defence against Toxoplasma gondii infection in the brain

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Blackwell Science Inc

RESUMO

Signal transducer and activator of transcription (STAT) 6 is a molecule involved in interleukin (IL)-4 and-13 signalling. We investigated the role of STAT6 signalling in Toxoplasma gondii-infected mice using STAT6-deficient (STAT6−/−) and wild-type (WT) mice. A significantly larger number of cysts were recovered from the brain in STAT6−/− than in WT mice on days 28 and 56 post-infection. CD8+ T cells in cerebrospinal fluid and spleen stimulated with T. gondii antigen produced higher levels of interferon (IFN)-γ in WT than in STAT6−/− mice. CD8+ T-cell function, estimated by expression of CD25 and cytotoxic activity, was lower in STAT6−/− than in WT mice. Transfer of CD8+ but not CD4+ T cells, purified from infected WT mice, into STAT6−/− mice successfully prevented formation of cysts in the brain. However, transfer of naïve CD8+ T cells from WT into STAT6−/− mice did not show either activation of CD8+ T cells or a decrease in the number of cysts in the brain. Transfer of splenic adherent cells from WT into STAT6−/− mice induced activation of CD8+ T cells and decreased the number of cysts in the brain. Expression of CD86 on splenic dendritic cells and IL-12 p40 production were weaker in STAT6−/− than in WT mice after T. gondii infection. These results indicate that STAT6 signalling is important in CD8+ T-cell activation, possibly through regulation of antigen-presenting cells, which could suppress T. gondii infection in the brain.

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