Author: Xu L, Yin W, Sun R, Wei H, Tian Z.
Abstract: The liver is considered as a unique lymphoid organ favoring the induction of immune tolerance rather than immunity. Biologists and clinicians alike have a long-standing interest in how liver induces systemic immune tolerance, but the mechanism has not yet been well elucidated. Here, we employed HBV-carrier mice generated by hydrodynamically injecting pAAV/HBV1.2 plasmid as a model for adult chronic HBV infection, which we found were unable to respond to HBsAg vaccination. Humoral tolerance induced in HBV- carrier mice could be transferred into Rag1-/- mice, since anti-HBV immunity in immunologically reconstituted Rag1-/- mice were inhibited by adoptive transfer of splenocytes from HBV-carrier mice. The humoral tolerance need at least 7 days for induction and persist to 3 months after a single HBV plasmid injection. Kupffer cell depletion or IL-10 deficiency broke this humoral tolerance, and exogenous injection of IL-10 could effectively induce this tolerance. Meanwhile, KCs in HBV-carrier mice expressed more IL-10 and mediated the systemic tolerance induction in an IL-10-dependent manner. This previously un-described humoral tolerance about HBV infection will help to explore new approaches to reverse liver-sustained systemic immune tolerance in liver disease.
Hepatology. 2013 Aug 8. doi: 10.1002/hep.26668.
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