| First Author | Washburn ML | Year | 2010 |
| Journal | PLoS One | Volume | 5 |
| Issue | 5 | Pages | e10585 |
| PubMed ID | 20498840 | Mgi Jnum | J:160829 |
| Mgi Id | MGI:4455233 | Doi | 10.1371/journal.pone.0010585 |
| Citation | Washburn ML, et al. (2010) LIGHT induces distinct signals to clear an AAV-expressed persistent antigen in the mouse liver and to induce liver inflammation. PLoS One 5(5):e10585 |
| abstractText | BACKGROUND: Infection with adeno-associated virus (AAV) vector with liver tropism leads to persistent expression of foreign antigens in the mouse liver, with no significant liver inflammation or pathology. This provides a model to investigate antigen persistence in the liver and strategies to modulate host immunity to reduce or clear the foreign antigen expressed from AAV vector in the liver. METHODS/PRINCIPAL FINDINGS: We showed that expressing LIGHT with an adenovirus vector (Ad) in mice with established AAV in the liver led to clearance of the AAV. Ad-LIGHT enhanced CD8 effector T cells in the liver, correlated with liver inflammation. LTbetaR-Ig proteins blocked Ad-LIGHT in clearing AAV. Interestingly, in LTbetaR-null mice, Ad-LIGHT still cleared AAV but caused no significant liver inflammation. CONCLUSIONS/SIGNIFICANCE: Our data suggest that LIGHT interaction with the LTbetaR plays a critical role in liver inflammation but is not required for LIGHT-mediated AAV clearance. These findings will shed light on developing novel immuno-therapeutics in treating people chronically infected with hepato-tropic viruses. |
