HEIGHTENED INTRAGRAFT CTL GENE-EXPRESSION IN ACUTELY REJECTING RENAL-ALLOGRAFTS

The role of CTL in the immunopathogenesis of acute cellular rejection is controversial. To further define the relationship of activated CTLs to rejection, we analyzed gene expression of three CTL-derived effect or molecules in renal allograft biopsies. CTLs are endowed with the ab ility to promote allograft damage through the elaboration of these hig hly cytopathic molecules. Intragraft gene transcript levels were deter mined for granzyme B, perforin, and TIA-1 and correlated with the immu nologic status of the allograft as categorized by conventional clinica l and histologic criteria. The categories were acute cellular rejectio n, chronic rejection, elements of both acute and chronic rejection, an d no evidence of rejection. Biopsies were snap-frozen, total RNA extra cted, and the mRNA converted to cDNA by reverse transcription. Levels were quantitated by competitive template PCR techniques. Intragraft gr anzyme B and perforin transcripts were highly restricted to biopsies i n the acute cellular rejection category. TIA-1 expression was more ubi quitous but significantly higher transcript levels were found in the a cute rejection category. The presence of these transcripts in acute ce llular rejection samples implicates CTL in the pathogenesis. Moreover, intragraft CTL-specific transcript levels may serve as markers of rej ection.