T cell subsets in experimental lupus nephritis: modulation by bacterial superantigen.
Chronic graft-vs-host disease (GvH), induced by injection of DBA/2 lymphocytes into (C57BL/6 x DBA/2)F1 hybrids, is a murine model for lupus nephritis, associated with a Th2-dependent polyclonal B cell activation. The development of glomerulosclerosis in this model is preceded by a glomerular influx of LFA-1+ T cells. We investigated whether exposure to bacterial superantigen would modulate the course of this autoimmune syndrome. Injection of the bacterial superantigen staphylococcal enterotoxin B (SEB) in mice has been shown to induce the activation of TcRVbeta8+ T cells. Within 2 weeks after GvH induction, mice were injected twice with 20 microg of SEB and the following parameters were examined: cytokine and Ig profile, proteinuria and renal pathology. The second SEB injection induced in GvH mice an increased release of both interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) as compared with control F1 mice. No differences were observed in IL-2 production. SEB-treated GvH mice demonstrated a delayed onset of proteinuria. Histological analysis of the kidney showed that SEB-challenged GvH mice displayed significantly more interstitial inflammation and mesangial proliferation together with more IgG2a deposits in glomeruli than non-injected GvH mice. From these results, we conclude that GvH mice are more responsive to SEB in terms of cytokine production and that bacterial infection can modulate the course of this renal disease from a membranous to a more proliferative type of nephropathy.
Leiden University Medical Center, Department of Pathology, The Netherlands.
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De Heer
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Aaldering
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Florquin
D000818:Animals; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004768:Enterotoxins / Q000494:pharmacology*; D006086:Graft vs Host Disease / Q000378:metabolism / Q000473:pathology; D007132:Immunoglobulin Isotypes / Q000378:metabolism; D007267:Injections; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism; D008181:Lupus Nephritis / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000473:pathology*
D016207:Cytokines; D004768:Enterotoxins; D007132:Immunoglobulin Isotypes; C031818:enterotoxin B, staphylococcal