Regulatory gamma delta T cells in Heymann nephritis express an invariant Vgamma6/Vdelta1 with a canonical CDR3 sequence.
Gammadelta 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 gammadelta T cells use a restricted set of gammadelta T cell receptor (TCR) genes. To explore whether this phenomenon of post injury expansion of gammadelta T cells occurs in autoimmune-mediated glomerulonephritis, we studied gammadelta TCR genes in Heymann nephritis (HN). Gammadelta T cells were increased in HN kidneys (p<0.001). These gammadelta T cells predominantly expressed Vgamma6/Vdelta1 genes and used canonical matching sequences previously seen in the other models of renal injury. Gammadelta T cells from the kidneys expressed high levels of TGF-beta, IL-4 and IL-5. The gammadelta T cells from both ADR-treated and HN kidneys expressed NKG2D, the NK cell-activating receptor. These results demonstrate that the majority of gammadelta T cells in the HN kidney use a canonical Vgamma6/Vdelta1 TCR--the gammadelta TCR previously described in the rat ADR-treated kidney. The restriction in gammadelta TCR seen in two completely different models of kidney injury and the expression of an innate activating molecule NKG2D suggests that the gammadelta T cells may be responding to tissue stress from injury and producing a regulatory response.
Wu
Huiling
H
Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia. huilingwu@med.usyd.edu.au
Knight
John F
JF
Alexander
Stephen I
SI
D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005921:Glomerulonephritis / Q000276:immunology*; D007668:Kidney / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D055655:NK Cell Lectin-Like Receptor Subfamily K; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016207:Cytokines; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D016212:Transforming Growth Factor beta