P-glycoprotein and alloimmune T-cell activation

Abstract

P-glycoprotein (P-gp), the human multidrug resistant (MDR1) gene product and cancer multidrug resistance-associated adenosine triphosphate (ATP)-binding cassette (ABC) transporter, is physiologically expressed on peripheral blood mononuclear cells, but its role in cellular immunity is only beginning to be elucidated. A role of P-gp in the secretion of several T-cell and antigen presenting cell-derived cytokines has been described, and additional functions of the molecule have been identified in lymphocyte survival and antigen presenting cell differentiation. Taken together, these findings provide compelling evidence that P-gp serves several distinct functions in the initiation of primary immune responses, and a critical role of the molecule in functional alloimmune responses is now established. Here, we will review the current understanding of P-gp function in alloimmune T-cell activation via both T-cell and antigen presenting cell-dependent mechanisms, which is relevant to the field of clinical transplantation, where P-gp has been found to be a marker of acute and chronic allograft rejection. Indeed, current in vitro findings raise the possibility that P-gp could represent a novel therapeutic target in acute and chronic allograft rejection, the major causes of allograft dysfunction and ultimate graft loss.