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Basic Immunology and Pathology |

T Cells Exacerbates Murine Adriamycin Nephropathy


* Centre for Kidney Research, Children's Hospital at Westmead,
Department of Renal Medicine, Royal Prince Alfred Hospital, and
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 
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 
T cells in this setting is unknown. This study examined the functional role of 
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. 
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 
T cells in AN kidney correlated positively with serum creatinine and glomerular sclerosis. The V
T cell receptor (TCR) repertoire in kidney showed expansion of a subset of cells that expressed V
6/V
1 genes and that used canonical TCR V
6/V
1 sequences in the CDR3 region of the TCR. 
T cells that were sorted from the kidneys expressed TGF-
but not IL-4, IL-10, or IFN-
. 
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 
T cells using antiTCR 
antibody resulted in worsening of serum creatinine, glomerulosclerosis, and interstitial inflammation. These studies indicate the involvement of the 
T cell in innate recognition and regulation of inflammation in AN.
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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673