THE STRONG CORRELATION OF CYTOTOXIC T LYMPHOCYTE-SPECIFIC SERINE PROTEASE GENE TRANSCRIPTS WITH RENAL ALLOGRAFT REJECTION1,2

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Abstract
Several immune mechanisms are likely to be responsible for renal allograft rejection. The relative importance of delayed-type hypersensitivity versus cytotoxic T lymphocytes is controversial. We analyzed human renal allografts biopsies for intragraft expression of IL-1 beta, IL-6, and TNF alpha genes--putative mediators of DTH--as well as IL-2, IL-2 receptor (R) beta, and a CTL-specific serine protease gene. Total RNA was extracted from tissue samples and the mRNA fraction was converted to cDNA using oligo dT and reverse transcriptase. Then cDNA was amplified by the polymerase chain reaction (PCR) for 35 cycles using specific oligonucleotide primers. Each PCR analysis included beta-actin oligonucleotide primers to coamplify this constitutively expressed gene as an internal control. A total of 24 core allograft biopsies were studied and classified into a 3 histological categories: acute cellular rejection, equivocal components of rejection, and no evidence of rejection. There was no statistically significant difference in beta-actin expression among these histologic categories (P greater than 0.08). Interestingly, in this sample size, no significant difference was found between rejecting and nonrejecting samples for transcripts of any of the cytokines or IL-2R beta mRNAs. Apparently, DTH-like mechanisms are present in all allografts. However, detection of CTL-specific serine protease gene expression was almost exclusive to rejecting samples (P less than 0.003). These findings suggest that activation of CTLs play an active, but hardly exclusive, role as effectors of graft dysfunction in the rejection process. While this study does not define the relative importance of the genes examined, it does suggest that evidence of CTL-specific serine protease expression may provide a means of monitoring for rejection episodes or as a diagnostic aid when conventional diagnostic criteria are not conclusive.