Clinical rejection is distinguished from subclinical rejection by increased infiltration by a population of activated macrophages

It has been reported previously that one-third of protocol renal biopsies i n asymptomatic, biochemically stable renal transplant recipients in the fir st 6 mo show unsuspected subclinical graft rejection (both infiltrate and t ubulitis) and that subclinical rejection is a risk factor for chronic renal dysfunction. This study was performed to determine whether differences in phenotype or activation status of graft-infiltrating cells underlie these d ifferent manifestations of acute rejection. Biopsies with normal histology (n = 10), subclinical rejection (n = 13), and clinical rejection (n = 9) we re studied using immunohistochemistry and computerized image analysis. Subc linical and clinical rejections had similar histologic Banff scores. Univar iate analysis showed a trend for a higher infiltration with CD8+ (P = 0.053 ) and CD68+ (P = 0.06) cells in clinical rejection, Of the activation marke rs studied (CD25, perforin, tumor necrosis factor-alpha), only allograft in flammatory factor-1+-activated macrophages were significantly (P = 0.014) i ncreased in the infiltrate of clinical rejection biopsies. These data sugge st that activated macrophages or their products are responsible for acute r enal dysfunction associated with clinical rejection episodes.