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Published ahead of print on February 28, 2007
J Am Soc Nephrol 18: 1180-1189, 2007
© 2007 American Society of Nephrology
doi: 10.1681/ASN.2006060622

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Basic Immunology and Pathology

Depletion of {gamma}{delta} T Cells Exacerbates Murine Adriamycin Nephropathy

Huiling Wu*,{dagger}, Yuan Min Wang*, Yiping Wang{ddagger}, Min Hu*, Geoff Yu Zhang*, John F. Knight*, David C.H. Harris{ddagger} and Stephen I. Alexander*

* Centre for Kidney Research, Children's Hospital at Westmead, {dagger} Department of Renal Medicine, Royal Prince Alfred Hospital, and {ddagger} Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute, Sydney, New South Wales, Australia

Address correspondence to: Dr. Stephen I. Alexander, Centre For Kidney Research, The Children's Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Australia. Phone: +612-9845-3430; Fax: +612-9845-3432; E-mail: stephena{at}chw.edu.au

Received for publication June 16, 2006. Accepted for publication January 17, 2007.

It has been reported that the presence of {gamma}{delta} 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 {gamma}{delta} T cells in this setting is unknown. This study examined the functional role of {gamma}{delta} 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. {gamma}{delta} 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 {gamma}{delta} T cells in AN kidney correlated positively with serum creatinine and glomerular sclerosis. The V{gamma}{delta} T cell receptor (TCR) repertoire in kidney showed expansion of a subset of cells that expressed V{gamma}6/V{delta}1 genes and that used canonical TCR V{gamma}6/V{delta}1 sequences in the CDR3 region of the TCR. {gamma}{delta} T cells that were sorted from the kidneys expressed TGF-beta but not IL-4, IL-10, or IFN-{gamma}. {gamma}{delta} 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 {gamma}{delta} T cells using anti–TCR {gamma}{delta} antibody resulted in worsening of serum creatinine, glomerulosclerosis, and interstitial inflammation. These studies indicate the involvement of the {gamma}{delta} T cell in innate recognition and regulation of inflammation in AN.




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