Depletion of γδ T Cells Exacerbates Murine Adriamycin Nephropathy

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Abstract
It has been reported that the presence of γδ T cells in kidney is associated with kidney damage in human IgA nephropathy and in rat models of chronic renal injury, including Adriamycin nephropathy (AN), but the functional role of γδ T cells in this setting is unknown. This study examined the functional role of γδ T cells in tissue injury in a murine model of AN. Murine AN was induced in BALB/c mice by a single injection of Adriamycin. γδ T cells as a proportion of CD3+ T cells were significantly increased in AN kidneys (16.8 ± 3.9%) but not in lymph nodes (1.3 ± 0.8%; P < 0.001). The proportion of γδ T cells in AN kidney correlated positively with serum creatinine and glomerular sclerosis. The Vγδ T cell receptor (TCR) repertoire in kidney showed expansion of a subset of cells that expressed Vγ6/Vδ1 genes and that used canonical TCR Vγ6/Vδ1 sequences in the CDR3 region of the TCR. γδ T cells that were sorted from the kidneys expressed TGF-β but not IL-4, IL-10, or IFN-γ. γδ T cells also expressed the activating receptor NKG2D and the NKG2D adaptor molecule DAP12. RAE-1, a ligand of NKG2D, was upregulated in AN kidney. Depletion of γδ T cells using anti–TCR γδ antibody resulted in worsening of serum creatinine, glomerulosclerosis, and interstitial inflammation. These studies indicate the involvement of the γδ T cell in innate recognition and regulation of inflammation in AN.