B7.1 and B7.2 co-stimulatory molecules regulate crescentic glomerulonephritis.

The contribution of B7.1 and B7.2 co-stimulation to Th1-directed, cell-mediated renal injury was studied in a murine model of crescentic glomerulonephritis (GN) initiated by a "planted" antigen. Mice treated with anti-B7.2 monoclonal antibody (mAb), starting prior to disease initiation, developed more severe renal injury with increased glomerular crescent formation (p = 0.031), glomerular accumulation of T cells (p = 0.014) and proteinuria (p = 0.022) compared to mice treated with control antibodies. Mice treated with anti-B7.1 mAb had reduced crescent formation (p = 0.019) compared to control treated mice, but reductions in glomerular CD4(+) T cell accumulation and proteinuria were not statistically significant. B7. 1 mAb treatment significantly reduced all parameters of renal injury (above) compared to anti-B7.2 mAb treatment. Neither treatment altered the circulating antibody titer or cutaneous delayed type hypersensitivity to the nephritogenic antigen. Antibody subclasses and antigen-stimulated ex vivo splenocyte IL-4, IL-10 and IFN-gamma production did not indicate effects on Th subset responses. Treatment with CTLA4-Fc or combined treatment with anti-B7.1 and B7. 2 antibodies did not significantly attenuate crescentic GN. These data indicate that B7.1 and B7.2 are important co-stimulatory molecules involved in crescentic GN, which have opposing effects on disease development without altering the T helper cell subset response to the nephritogenic antigen.