Depletion of gammadelta T cells exacerbates murine adriamycin nephropathy.
J Am Soc Nephrol
; 18(4): 1180-9, 2007 Apr.
Article
em En
| MEDLINE
| ID: mdl-17329577
ABSTRACT
It has been reported that the presence of gammadelta 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 gammadelta T cells in this setting is unknown. This study examined the functional role of gammadelta 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. gammadelta 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 gammadelta T cells in AN kidney correlated positively with serum creatinine and glomerular sclerosis. The Vgammadelta T cell receptor (TCR) repertoire in kidney showed expansion of a subset of cells that expressed Vgamma6/Vdelta1 genes and that used canonical TCR Vgamma6/Vdelta1 sequences in the CDR3 region of the TCR. gammadelta T cells that were sorted from the kidneys expressed TGF-beta but not IL-4, IL-10, or IFN-gamma. gammadelta 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 gammadelta T cells using anti-TCR gammadelta antibody resulted in worsening of serum creatinine, glomerulosclerosis, and interstitial inflammation. These studies indicate the involvement of the gammadelta T cell in innate recognition and regulation of inflammation in AN.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Doxorrubicina
/
Receptores de Antígenos de Linfócitos T gama-delta
/
Nefropatias
Limite:
Animals
Idioma:
En
Revista:
J Am Soc Nephrol
Assunto da revista:
NEFROLOGIA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Austrália