B7 costimulation in the development of lupus: autoimmunity arises either in the absence of B7.1/B7.2 or in the presence of anti-B7.1/B7.2 blocking antibodies

Costimulatory molecules, termed B7.1 and B7.2, are present on the surfaces of APC and are important for the activation of T lymphocytes specific for b oth foreign Ags and autoantigens. We have examined the role of B7 costimula tion in the MRL-lpr/lpr murine model of human systemic lupus erythematosus, MRL-lpr/lpr mice receiving both anti-B7.1 and anti-B7.2 Abs expressed sign ificantly lower anti-small nuclear ribonucleoprotein particles (snRNP) and anti-dsDNA autoantibodies than did untreated mice, Anti-B7.2 Ab treatment a lone inhibited anti-dsDNA autoantibody expression while having no effect on anti-snRNP autoantibody expression. Anti-B7.1 Ab treatment alone did not c hange the expression of either anti-snRNP or anti-dsDNA autoantibodies. Par allel studies performed in MRL-lpr/lpr mice genetically deficient in either B7.1 or B7.2 expressed autoantibody profiles comparable to those found in wild-type MRL-lpr/lpr mice. However, B7.1-deficient MRL-lpr/lpr mice exhibi ted distinct and more severe glomerulonephritis while B7.2-deficient MRL-lp r/lpr mice had significantly milder or absent kidney pathology as compared with age-matched wild-type mice. These studies indicate that each B7 costim ulatory signal may control unique pathological events in murine systemic lu pus erythematosus that may not always be apparent in autoantibody titers al one.