Pendse Shona S, Briscoe David M, Frank Markus H
Laboratory of Immunogenetics and Transplantation, Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Clin Appl Immunol Rev. 2003 Jul;4(1):3-14. doi: 10.1016/S1529-1049(03)00007-2.
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.
P-糖蛋白（P-gp）是人类多药耐药（MDR1）基因产物，也是与癌症多药耐药相关的三磷酸腺苷（ATP）结合盒（ABC）转运蛋白，它在外周血单个核细胞上有生理性表达，但其在细胞免疫中的作用才刚刚开始被阐明。P-糖蛋白在几种T细胞和抗原呈递细胞衍生的细胞因子分泌中的作用已被描述，并且该分子在淋巴细胞存活和抗原呈递细胞分化中还具有其他功能。综上所述，这些发现提供了令人信服的证据，表明P-糖蛋白在原发性免疫反应的启动中发挥多种不同功能，并且该分子在功能性同种异体免疫反应中的关键作用现已确立。在此，我们将综述目前对P-糖蛋白通过T细胞和抗原呈递细胞依赖性机制在同种异体免疫T细胞活化中的功能的理解，这与临床移植领域相关，在该领域中，P-糖蛋白已被发现是急性和慢性同种异体移植排斥反应的标志物。事实上，目前的体外研究结果表明，P-糖蛋白有可能成为急性和慢性同种异体移植排斥反应的新型治疗靶点，而急性和慢性同种异体移植排斥反应是同种异体移植功能障碍和最终移植失败的主要原因。
