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 effector molecules in renal allograft biopsies. CTLs are endowed with the ability to promote allograft damage through the elaboration of these highly cytopathic molecules. Intragraft gene transcript levels were determined for granzyme B, perforin, and TIA-1 and correlated with the immunologic status of the allograft as categorized by conventional clinical and histologic criteria. The categories were acute cellular rejection, chronic rejection, elements of both acute and chronic rejection, and no evidence of rejection. Biopsies were snap-frozen, total RNA extracted, and the mRNA converted to cDNA by reverse transcription. Levels were quantitated by competitive template PCR techniques. Intragraft granzyme B and perforin transcripts were highly restricted to biopsies in the acute cellular rejection category. TIA-1 expression was more ubiquitous but significantly higher transcript levels were found in the acute rejection category. The presence of these transcripts in acute cellular rejection samples implicates CTL in the pathogenesis. Moreover, intragraft CTL-specific transcript levels may serve as markers of rejection.
Lipman
M L
ML
Department of Medicine, Beth Israel Hospital, Boston, MA 02215.
Stevens
A C
AC
Strom
T B
TB
D001483:Base Sequence; D015870:Gene Expression; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006084:Graft Rejection; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D054353:Perforin; D039102:Poly(A)-Binding Proteins; D016133:Polymerase Chain Reaction; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; D016601:RNA-Binding Proteins / Q000235:genetics; D000074019:T-Cell Intracellular Antigen-1; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D014184:Transplantation, Homologous
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D039102:Poly(A)-Binding Proteins; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D054353:Perforin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases