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- W2092983498 abstract "Introduction: Recently, we have demonstrated that sublethal doses of concanavalin A (ConA) induce tolerance towards ConA hepatitis in mice within one week. Tolerance is mediated by IL-10 producing regulatory T cells (Tregs). In vivo and in vitro data suggested that highly suppressive ConA-primed Foxp3+ Tregs might convert naïve CD4+ T cells into immunosuppressive Foxp3+ T cells. Hence, this study was intended to identify the relevance of “infectious tolerance“ as one mechanism of ConA tolerance. Methods: Splenic CD4+ T cells from DEREG (“depletion of regulatory T cells“) mice were co-cultivated with splenic Tregs from saline- or ConA-pretreated wt mice. Moreover, liver non-parenchymal cells (NPCs) or total splenocytes were isolated from DEREG mice. Cells were stimulated with anti-CD3 mAb for 72hrs. Foxp3 expression correlating with GFP expression and expression of surface markers with suppressive/regulatory function were quantified by FACS analysis. Results: Tregs from ConA- or saline-treated mice could not induce Foxp3 expression in the co-culture system. However, a transient FoxP3/GFP expression was detectable in cultures of whole splenocytes and liver NPCs, respectively, suggesting the requirement of APCs in Treg conversion. PD1, CCR5, and CXCR3 expression were upregulated on Tregs from ConA-treated mice, whereas CD45RB and CD62L were downregulated. Conclusion: Different migration patterns and surface expression profiles seem to characterize highly suppressive ConA-primed Tregs. Moreover, conversion of naïve T cells into Foxp3+ T cells by Tregs alone might be of minor importance for controlling ConA-induced inflammation; however, differentiation of IL-10 secreting FoxP3-negative Tr1 cells might be induced by Tregs in an infectious manner. Further studies will identify the mechanism of the transient FoxP3 expression upon ConA challenge in vivo and the potential of liver-specific APCs, e.g. LSECs or hepatocytes to convert naïve intrahepatic T cells into Tregs." @default.
- W2092983498 created "2016-06-24" @default.
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- W2092983498 date "2010-01-01" @default.
- W2092983498 modified "2023-09-26" @default.
- W2092983498 title "Conversion of naïve T Cells into regulatory T Cells after tolerance induction in the murine liver" @default.
- W2092983498 doi "https://doi.org/10.1055/s-0029-1246504" @default.
- W2092983498 hasPublicationYear "2010" @default.
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