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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antineoplastic Agents / pharmacology
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Blood Vessels / immunology
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Blood Vessels / metabolism
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Cells, Cultured
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Chemokine CCL4
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Chemokine CCL5 / genetics
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Chemokine CCL5 / metabolism
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Chemokine CXCL10
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Chemokine CXCL11
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Chemokine CXCL9
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Chemokines, CXC / genetics
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Chemokines, CXC / metabolism
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Endothelial Cells / immunology
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Endothelial Cells / metabolism
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Graft Rejection / etiology*
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Heart Transplantation / immunology*
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Humans
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / metabolism
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Interferon-gamma / pharmacology*
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Leukocytes
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Macrophage Inflammatory Proteins / genetics
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Macrophage Inflammatory Proteins / metabolism
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Muscle, Smooth, Vascular / immunology
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Muscle, Smooth, Vascular / metabolism
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RNA, Messenger / analysis
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Receptors, CCR5 / immunology
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Receptors, CCR5 / metabolism*
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Receptors, CXCR3
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Receptors, Chemokine / immunology
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Receptors, Chemokine / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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Transplantation, Homologous
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Vascular Diseases / etiology*
Substances
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Antineoplastic Agents
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CXCL11 protein, human
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CXCL9 protein, human
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CXCR3 protein, human
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Chemokine CCL4
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Chemokine CCL5
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Chemokine CXCL10
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Chemokine CXCL11
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Chemokine CXCL9
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Chemokines, CXC
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Cxcl11 protein, mouse
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Cxcr3 protein, mouse
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Intercellular Signaling Peptides and Proteins
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Macrophage Inflammatory Proteins
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RNA, Messenger
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Receptors, CCR5
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Receptors, CXCR3
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Receptors, Chemokine
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Interferon-gamma