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Infiltration of Canonical Vγ4/Vδ1 γδ T Cells in an Adriamycin-Induced Progressive Renal Failure Model1

We have previously reported an infiltration of renal interstitial γδ T cells in Adriamycin-induced progressive glomerulosclerosis in the rat kidney. The TCR repertoire and sequences used by these γδ T cells have now been studied. Two injections of Adriamycin 14 days apart caused segmental glomerulosclerosis, massive interstitial infiltration of mononuclear cells, and end-stage renal failure. Flow cytometry of lymphocyte subpopulations with Abs to CD3, the γδ TCR, and the αβ TCR showed that γδ T cells as a proportion of CD3+ cells were increased in Adriamycin-treated kidneys (8.5 ± 5.4%), but not in lymph nodes (1.3 ± 0.4%). A semiquantitative score of glomerular damage (r = 0.65; p < 0.01) and creatinine (r = 0.62; p < 0.01) correlated significantly with the presence of γδ T cells. TCR Vγ repertoire analysis by RT-PCR and Southern blotting showed that Vγ2 was the dominant subfamily in lymph nodes, whereas Vγ4 became the predominant subfamily in advanced stages of the rat Adriamycin-treated kidney. Sequencing of the Vγ4-Jγ junctional region showed an invariant sequence. The amino acid sequence of the junctional region of the Vγ4 TCR was the same as the reported mouse canonical Vγ4 TCR sequence. Analysis of the kidney Vδ repertoire showed dominant expression of Vδ1, and sequencing again revealed the selective expression of a canonical Vδ1 gene. Semiquantitative RT-PCR for cytokine gene expression showed that γδ T cells from the kidneys expressed TGF-β, but not IL-4, IL-10, or IFN-γ. These results suggest that the predominant γδ T cells in the Adriamycin kidney use an invariant Vγ4/Vδ1 receptor.