Blockade of inducible costimulator pathway to prevent acute rejection in rat liver transplantation.

Background: The role of inducible costimulator (ICOS) in transplantation immunity remains unclear.

Methods: A Lewis-to-Brown-Norway (BN) rat liver transplant model was used to explore the effect of ICOS blockade by small interference RNA. Recipient survival rate, number of CD25/ICOS-positive cells, ICOS mRNA and protein levels, and interferon-gamma and tumor-necrosis factor-alpha levels were determined.

Results: Recipient survival was significantly prolonged in rats treated with RNA interference. On day 7 after transplantation, there was a diminished frequency of CD25/ICOS-positive cells and an increased frequency of apoptotic T cells. Furthermore, we found that ICOS blockade could inhibit mRNA and protein expression of ICOS, decrease plasma levels of interferon-gamma and tumor-necrosis factor-alpha, suppress cell infiltration into grafts, and promote tolerance in the interference group.

Conclusions: Our data demonstrate that RNA interference is a potent tool to down-modulate ICOS expression and protect allografts from acute rejection.