| First Author | Wiegard C | Year | 2007 |
| Journal | Gastroenterology | Volume | 133 |
| Issue | 6 | Pages | 2010-8 |
| PubMed ID | 17967458 | Mgi Jnum | J:135514 |
| Mgi Id | MGI:3793981 | Doi | 10.1053/j.gastro.2007.09.007 |
| Citation | Wiegard C, et al. (2007) Defective T helper response of hepatocyte-stimulated CD4 T cells impairs antiviral CD8 response and viral clearance. Gastroenterology 133(6):2010-8 |
| abstractText | BACKGROUND & AIMS: In hepatitis, hepatocytes gain the ability to express major histocompatibility complex (MHC) class II molecules and to present antigen to CD4 T cells. Here, we investigated whether MHC class II-expressing hepatocytes influence in vitro the differentiation of CD4 T cells and in vivo the T-cell response to and control of viral infection. METHODS: Class II transactivator-transgenic hepatocytes that constitutively express MHC class II molecules were used to stimulate CD4 T cells in vitro, and the effector response type of the stimulated CD4 T cells was determined. The in vivo relevance of the obtained findings was confirmed by infecting nontransgenic or class II transactivator-transgenic mice with lymphocytic choriomeningitis virus. RESULTS: MHC II-expressing hepatocytes induced T helper cell (Th) 2 differentiation of uncommitted CD4 T cells and abrogated the ability of previously differentiated Th1 to secrete interferon-gamma, even in the presence of proinflammatory microbial signals. The suppression of Th1 responses by hepatocytes was associated with poor expression levels of Th1-promoting Delta-like Notch ligands. In vivo, MHC II expression by hepatocytes impaired the interferon-gamma production by lymphocytic choriomeningitis virus-specific CD4 and CD8 T cells and prolonged viral persistence. CONCLUSIONS: By instructing infiltrating CD4 T cells to differentiate into a less inflammatory phenotype, MHC II-expressing hepatocytes seem to impair antiviral CD8 T-cell responses and viral clearance. Thus, hepatocytes may contribute to the chronicity of hepatitis virus infection. |
