Expression of the chemokine receptor CXCR3 in human renal allografts--a prospective study.
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.
Hoffmann
Ute
U
Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Germany. Ute.hoffmann@klinik.uni-regensburg.de
Segerer
Stephan
S
Rümmele
Petra
P
Krüger
Bernd
B
Pietrzyk
Miriam
M
Hofstädter
Ferdinand
F
Banas
Bernhard
B
Krämer
Bernhard K
BK
D015415:Biomarkers / Q000032:analysis*; D001707:Biopsy, Needle; D016022:Case-Control Studies; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival; D006801:Humans; D007150:Immunohistochemistry; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology* / Q000379:methods; D008297:Male; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism*; D012680:Sensitivity and Specificity; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D015415:Biomarkers; C515187:CXCR3 protein, human; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine