Regulatory gamma delta T cells in Heymann nephritis express an invariant Vγ6/Vδ1 with a canonical CDR3 sequence

Abstract

γδ T cells are expanded in human IgA nephropathy and in a rat model of adriamycin (ADR)-induced nephropathy. Despite different diseases and species, these renal γδ T cells use a restricted set of γδ T cell receptor (TCR) genes. To explore whether this phenomenon of post injury expansion of γδ T cells occurs in autoimmune-mediated glomerulonephritis, we studied γδ TCR genes in Heymann nephritis (HN). γδ T cells were increased in HN kidneys (P<0.001). These γδ T cells predominantly expressed Vγ6/Vδ1 genes and used canonical matching sequences previously seen in the other models of renal injury. γ δ T cells from the kidneys expressed high levels of TGF-β, IL-4 and IL-5. The γδ T cells from both ADR-treated and HN kidneys expressed NKG2D, the NK cell-activating receptor. These results demonstrate that the majority of γδ T cells in the HN kidney use a canonical Vγ6/Vδ1 TCR - the γδ TCR previously described in the rat ADR-treated kidney. The restriction in γδ TCR seen in two completely different models of kidney injury and the expression of an innate activating molecule NKG2D suggests that the γδ T cells may be responding to tissue stress from injury and producing a regulatory response. © 2004 Wiley-VCH Verlag GmbH & Co. KGaA.