The Role of Toll-Like Receptors 2 and 4 in Acute Allograft Rejection After Liver Transplantation

Toll-like receptors (TLRs) are germline-encoded receptors expressed on antigen-presenting cells (APCs) that identify a variety of microbial and endogenous ligands and activate the innate immune responses to the presence of danger. However, their role in the development of allograft rejection after liver transplantation remains unknown. In this study, we used flow cytometry to assess TLR-4 and TLR-2 expression among circulating CD14+ monocytes in 64 liver transplant patients and 24 healthy volunteers. We demonstrated significantly higher TLR-2 and TLR-4 expression on circulating monocytes among conditioned liver transplantation recipients with acute rejection compared with those in clinically stable with normal liver function. Steroid pulse therapy significantly reduced the expression of TLR-4 and TLR-2 on the monocytes of recipients with acute rejection. Based on these data, we have suggested that activation of innate immunity in liver transplant recipients through TLR-4 and TLR-2 contributes to the development of acute allograft rejection after liver transplantation. The reduced expression of TLR-4 and TLR-2 may be one of the mechanisms by which steroid pulse therapy inhibits the development of acute rejection. Estimation of TLR expression on APCs may be predictive of in acute rejection after liver transplantation.