Chemokines in islet allograft rejection.

Chemokines have emerged as important regulators in the development, differentiation, and anatomic distribution of leukocytes. Studies of renal and cardiac allograft biopsies have revealed that the expression of many chemokine receptors and their ligands was associated with acute allograft rejection. However, the importance of these chemokine receptor systems varies in the host response to a particular allograft. In this regard, CXCR3 appears to play a more important role in cardiac allograft rejection than CCR2 and CCR5. We have found that CCR2, CCR5, and CXCR3 and their ligands, as well as Th1 cytokines are induced to high levels in rejecting islet allografts. Interestingly, targeting CCR5 resulted in a significant prolongation of islet allograft survival. This prolongation was associated with a Th2 response. Our data indicate that in the process of acute rejection, the temporal expression and the ultimate function of a given chemokine vary among different organs or tissues. Hence, each organ or tissue may require a unique set of chemokines to generate acute rejection. Targeting the appropriate chemokine receptors may provide a clinically useful strategy to prevent islet allograft rejection. Copyright 2003 John Wiley & Sons, Ltd.