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The Puzzling Role of CXCR3 and Its Ligands in Organ Allograft Rejection

Leukocyte trafﬁcking to and through the vascular endothe-lium and into parenchymal tissues during inﬂammation,with selective exclusion of some leukocytes from the in-ﬂamed site, reﬂects a complex series of molecular interac-tions involving adhesion and chemoattractant molecules.Chemokine mechanisms have attracted much interest astargets for preventing antigen-primed T cells and inﬂam-matory cells from inﬁltrating target tissues in allergy, au-toimmunity and transplantation. CXCR3 is expressed oneffector T cells inﬁltrating the allograft, and CXCR3 mRNAis prominent in acute rejection in cardiac and renal trans-plants. Similarly, the ligands for CXCR3—CXCL9, CXCL10and CXCL11—are abundant in rejecting allografts. Theseligands are regulated by interferon-