Recruitment of CXCR3+ and CCR5+ T cells and production of interferon-γ-inducible chemokines in rejecting human arteries

William R. Burns, Yinong Wang, Paul C.Y. Tang, Hooman Ranjbaran, Alexander Iakimov, Jinah Kim, Madison Cuffy, Yalai Bai, Jordan S. Pober, George Tellides

Research output: Contribution to journalArticlepeer-review

Abstract

Chemokine receptors preferentially expressed by Th1 cells and their IFN-γ-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-1β. 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-γ-secreting T cells to the vessel wall, and reinforce the suggestion that the arterial media may be a site of immunological privilege.

Original languageEnglish (US)
Pages (from-to)1226-1236
Number of pages11
JournalAmerican Journal of Transplantation
Volume5
Issue number6
DOIs
StatePublished - Jun 2005
Externally publishedYes

Keywords

  • Arteriosclerosis
  • Artery
  • Chemokines
  • T cells
  • Vascular remodeling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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