Depletion of gammadelta T cells exacerbates murine adriamycin nephropathy.
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.
Wu
Huiling
H
Centre For Kidney Research, The Children's Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Australia.
Wang
Yuan Min
YM
Wang
Yiping
Y
Hu
Min
M
Zhang
Geoff Yu
GY
Knight
John F
JF
Harris
David C H
DC
Alexander
Stephen I
SI
D000818:Animals; D016207:Cytokines / Q000235:genetics; D004317:Doxorubicin / Q000633:toxicity*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D055655:NK Cell Lectin-Like Receptor Subfamily K; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology*; D011971:Receptors, Immunologic / Q000235:genetics; D055607:Receptors, Natural Killer Cell; D013601:T-Lymphocytes / Q000502:physiology*
D016207:Cytokines; C492355:Hcst protein, mouse; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D034521:Nuclear Matrix-Associated Proteins; D029543:Nucleocytoplasmic Transport Proteins; C490521:Rae1 protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D004317:Doxorubicin