title: Recruitment of CXCR3+ and CCR5+ T cells and production of interferon-gamma-inducible chemokines in rejecting human arteries.
abstract: Chemokine receptors preferentially expressed by Th1 cells and their IFN-gamma-inducible ligands predominate in experimental and clinical allograft rejection. Previous chemokine-related transplantation studies have focused on parenchymal and microvascular inflammation which are of importance in acute rejection, but are not necessarily relevant in immune-mediated injury of conduit arteries. We have recently described a model of progressive human T cell-mediated infiltration and injury of allogeneic coronary artery segments using immunodeficient mouse hosts. In the present study, we investigated if recruitment of allogeneic T cells to different vascular compartments correlated with the expression of chemokines and their receptors. Transcripts were quantified by laser capture microdissection/real-time RT-PCR and their distribution was correlated to the corresponding protein expression detected by immunohistochemistry. Infiltrating T cells, confined to the adventitia and intima, expressed CXCR3 and CCR5, but were not recruited into the media despite production by vascular smooth muscle cells of IP-10, Mig, I-TAC, RANTES and MIP-1beta. Chemokine mRNA was detected primarily in vascular cells, although chemokine protein largely localized to infiltrating leukocytes which uniquely expressed their cognate receptors. These data explain the recruitment of IFN-gamma-secreting T cells to the vessel wall, and reinforce the suggestion that the arterial media may be a site of immunological privilege.
authors.affiliation: Interdepartmental Program in Vascular Biology and Transplantation, Boyer Center for Molecular Medicine, Department of Surgery, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Burns
authors.forename: Yinong
authors.initials: Y
authors.lastname: Wang
authors.forename: Paul C Y
authors.initials: PC
authors.lastname: Tang
authors.forename: Hooman
authors.initials: H
authors.lastname: Ranjbaran
authors.forename: Alexander
authors.initials: A
authors.lastname: Iakimov
authors.forename: Jinah
authors.initials: J
authors.lastname: Kim
authors.forename: Madison
authors.initials: M
authors.lastname: Cuffy
authors.forename: Yalai
authors.initials: Y
authors.lastname: Bai
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Pober
authors.forename: George
authors.initials: G
authors.lastname: Tellides
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001808:Blood Vessels / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D006084:Graft Rejection / Q000209:etiology*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D007962:Leukocytes; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous; D014652:Vascular Diseases / Q000209:etiology*
chemical_list: D000970:Antineoplastic Agents; C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; C515203:Cxcl11 protein, mouse; C515188:Cxcr3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma