Chemokine receptor (CXCR4) mRNA-expressing leukocytes are increased in human renal allograft rejection

Background. Mononuclear cell infiltration is a common feature of cell-media ted renal transplant rejection. Chemokines and their corresponding receptor s likely play a central role in directing specific classes of leukocytes to graft sites during rejection. Localization of chemokine receptors may help us understand how specificity in leukocyte trafficking is achieved in rena l inflammatory processes. The localization of the chemokine receptor CXCR4 in human kidney and in renal transplant rejection is unknown. Methods. We generated a riboprobe specific for the detection of CXCR4 mRNA by in situ hybridization to evaluate cellular sites of synthesis of this re ceptor in native human kidneys (n=11) and in human allograft nephrectomies with features of severe rejection (n=14), Results. By in situ hybridization, CXCR4 mRNA expression is undetectable in intrinsic glomerular, tubular, and renovascular cells in native kidneys, W hen renal interstitial inflammation is present, CXCR4 mRNA expression is lo calized to a large fraction of infiltrating leukocytes. Large numbers of CX CR4-expressing cells are detected in cell-mediated renal allograft rejectio n. Double immunolabeling: for CD3 antigen identified a large fraction of in filtrating CXCR4 mRNA-expressing cells as T lymphocytes. CXCR4 mRNA-express ing cells were frequently seen in neointimal lesions of vascular rejection in allograft nei phrectomies. CXCR4 mRNA expression was identified in infil trating neointimal T lymphocytes, but not smooth muscle cells by immunolabe ling. Conclusions. We demonstrate the involvement of CXCR4 mRNA-expressing infilt rating cells in human renal interstitial and vascular allograft rejection. Signaling via the CXCR4 receptor may be one mechanism by which chemokines m ediate leukocyte trafficking in renal allograft rejection.