NK cell stimulatory receptors and ligands are induced post‐transplantation

Studies suggest a role for NK cells in acute and chronic allograft rejection. Further we have shown that calcineurin inhibitors do not block NK cell function. NK cells express inhibitory receptors that bind to classical MHC class I molecules and prevent killing. NK cells also express stimulatory receptors that activate and/or regulate effector function. In the context of transplantation NK cells are a major source of IFNγ early post‐transplant, however the expression and functional significance of NK cell receptors in the alloimmune response remain unclear. Using an experimental model of rat liver transplantation we show by quantitative real‐time PCR (qPCR), that the stimulatory receptors NKp46 and NKG2D are increased in allografts, but not syngeneic grafts, by day 3 post‐transplant. Similarly, we have cloned two rat NKG2D ligands and demonstrate that their expression is silent in normal liver, induced upon liver transplantation, and specifically increased in allografts by day 3. In contrast, increased expression of the stimulatory receptor NKp30 is detected in allografts on the first day post‐transplant. Further, NKp30 mediates NK cell interaction with dendritic cells leading to abundant IFNγ production. Our data demonstrate the concomitant expression of NK receptors and induced ligands in allografts and suggests that NK cells are a functional link between innate and adaptive immunity post‐transplantation. Supported by NIH AI44095