NDT Advance Access originally published online on January 18, 2006
Nephrology Dialysis Transplantation 2006 21(5):1373-1381; doi:10.1093/ndt/gfk075
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Dialysis and Transplantation
Expression of the chemokine receptor CXCR3 in human renal allografts—a prospective study
1 Klinik und Poliklinik für Innere Medizin II, 3 Pathologisches Institut, Universität Regensburg and 2 Medizinische Poliklinik-Innenstadt, Klinikum der Universität, München, Germany
Correspondence and offprint requests to: Ute Hoffmann, MD, Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität, D-93042 Regensburg, Germany.Email: Ute.hoffmann{at}klinik.uni-regensburg.de
Background. Mechanisms involved in the recruitment and activation of inflammatory cells during renal allograft injury are still incompletely understood. Since chemokines play pivotal roles in this process, our prospective study was performed to evaluate further the role of the chemokine receptor CXCR3.
Methods. A total of 138 biopsies were included from patients without rejection and unaltered morphology (according to Banff 97 classification grade 1, n = 49), with acute interstitial rejection (Banff grade 4 type I, n = 8), with acute vascular rejection (Banff grade 4 type II, n = 23), with chronic allograft nephropathy (Banff grade 5, n = 16), without rejection but with various other lesions (Banff grade 6, n = 36) and from pre-transplant kidneys (n = 6). The expression of CXCR3-, CD4- and CD8-positive cells was localized by immunohistochemistry and quantified by image analysis.
Results. CXCR3 was expressed by infiltrating inflammatory cells, but not by intrinsic renal structures. CXCR3-positive cells were found to be involved in tubulitis and vascular rejection. The area of CXCR3-positive staining was significantly larger in biopsies with acute interstitial rejection (P<0.001) and acute vascular rejection (P<0.001) as compared with normal renal graft biopsies. There was a strong morphological and numerical correlation between CXCR3 and both CD4- and CD8-positive T cells, respectively.
Conclusions. A significant part of both CD4- and CD8-positive T cells express the chemokine receptor CXCR3. During renal allograft rejection, the number of these cells increases significantly at the site of injury and might be targeted by CXCR3 blocking agents.
Keywords: chemokine receptors; CXCR3; human renal allograft rejection; immunohistochemistry
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