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 language | English (US) |
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Pages (from-to) | 1226-1236 |
Number of pages | 11 |
Journal | American Journal of Transplantation |
Volume | 5 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2005 |
Externally published | Yes |
Keywords
- Arteriosclerosis
- Artery
- Chemokines
- T cells
- Vascular remodeling
ASJC Scopus subject areas
- Immunology and Allergy
- Transplantation
- Pharmacology (medical)