T cell subsets in experimental lupus nephritis: modulation by bacterial superantigen

Chronic graft-vs-host disease (GVH), induced by injection of DBA/2 lymphocy tes 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 develop ment of glomerulosclerosis in this model is preceded by a glomerular influx of LFA-1(+) T cells. We investigated whether exposure to bacterial superan tigen would modulate the course of this autoimmune syndrome. Injection of t he bacterial superantigen staphylococcal enterotoxin B (SEB) in mice has be en shown to induce the activation of TcRV beta 8(+) T cells. Within 2 weeks after GvH induction, mice were injected twice with 20 mu g of SEE and the following parameters were examined: cytokine and Ig profile, proteinuria an d renal pathology. The second SEE injection induced in GvH mice an increase d release of both interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) a s compared with control Fl mice. No differences were observed in IL-2 produ ction. SEE-treated GvH mice demonstrated a delayed onset of proteinuria. Hi stological analysis of the kidney showed that SEB-challenged GvH mice displ ayed significantly more interstitial inflammation and mesangial proliferati on together with more IgG2a deposits in glomeruli than non-injected GvH mic e. From these results, we conclude that GvH mice are more responsive to SEE 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.