imprint:
[Erscheinungsort nicht ermittelbar]: eScholarship, University of California, 2009
Language:
Not determined
Origination:
University thesis:
Dissertation, eScholarship, University of California, 2009
Footnote:
Description:
Transforming growth factor-[beta] (TGF-[beta]) has recently been identified as a critical inhibitory cytokine involved in the suppression of cytotoxic T cells during chronic viral infection with lymphocytic choriomeningitis virus (LCMV). Here, we provide further clarifications of its gene expression, protein production, activation, and signaling in the context of chronic infection. Our investigations suggest TGF-[beta] protein expression and bioavailability to cells is comparable during acute and chronic infection. However only chronically infected mice exhibit sustained TGF-[beta] bioactivity and protein levels at day 30-31 post infection. This prolonged expression suggests the cytokine may play an important role in viral persistence. We further provide evidence highlighting upregulation of TGF-[beta] gene expression in dendritic cells compared to other leukocyte populations during LCMV infection. More notably, we identify significant enhancements of uPAR, a key activator of TGF- [beta] bioactivity, gene expression in DCs uniquely during chronic infection. These findings suggest TGF-[beta] may be preferentially expressed and activated by chronically infected DCs through a distinctive pathway that can contribute to viral persistence. Altogether, our findings help to characterize TGF-[beta] specifically in an immunosuppressive environment induced by chronic viral infections in vivo