Simulating the effect of CTLA-4 competing with CD28 for B7, anti-CD28 was used to block CD28 signaling in NZB/NZW mice, which prevented lupus nephritis development, prolonged animal survival, reduced production of against double strand DNA (dsDNA) autoantibodies, and increased expression of IDO, receptor programmed cell-death-1 (PD-1), and ligand programmed death ligand-1 (PDL-1) (118). Here, CD28 is linked to lupus nephritis.