Study of CC chemokine receptor 5 in renal allograft rejection

Abstract

Allospecific recruitment of T cells is primary to the pathogenesis of renal transplant rejection. Chemokines and their receptors inducing a Th1 cytokine response play a central role in this recruitment. Renal allograft biopsies of 28 patients with acute cellular rejection and 10 protocol biopsies (controls) were examined in accordance with Banff grading 2007 schema. Immunohistochemistry for CD3 and CC chemokine receptor 5 (CCR5) in sequential sections was performed and quantitatively assessed in the glomeruli, tubules, and interstitium. Histopathologic and clinical correlations were carried out. CD3- and CCR5-positive cells were observed in significantly higher numbers in rejection cases than in controls (P = 0.010). A larger proportion of CCR5-positive cells were noted in the foci of tubulitis compared to the interstitial infiltrates and glomeruli in all cases, and it correlated with the grade of cellular rejection (P = 0.010). A greater number of CCR5-positive cells were seen in early rejection (<6 months posttransplant) compared to late rejection. No clinical correlation with serum creatinine levels was found. CCR5-positive cells represent the alloaggressive subset of T cells in ACR, and their numbers correlate with rejection severity. CCR5 may be used as a marker of early acute rejection and may be an important target for future antirejection therapies.