Inhibition of T cell activation and autoimmune diabetes using a B cell surface–linked CTLA-4 agonist
J. Clin. Invest. Brian T. Fife, et al. 116:2252 doi:10.1172/JCI27856 [Go to this article.]

Figure 7
scαCTLA-4 Tg⁺ NOD. B7 DKO mice are protected from accelerated diabetes. Female NOD.B7 DKO and NOD.B7 DKO.scαCTLA-4 Tg⁺ mice were monitored for the development of spontaneous disease. (A) Diabetes incidence is shown here for NOD.B7 DKO (n = 12) (open circles) and NOD.B7 DKO.scαCTLA-4 Tg⁺ mice (n = 20) (filled circles). NOD.B7 DKO diabetes incidence reached 100% while diabetes incidence in NOD.B7 DKO.scαCTLA-4 Tg⁺ mice was significantly reduced to 60% by 30 weeks of age (P < 0.003). (B) NOD.B7 DKO.scαCTLA-4 Tg⁺ mice have decreased insulitis at 14 weeks of age. Pancreas from 14-week-old NOD.B7 DKO and scαCTLA-4 Tg NOD.B7 DKO mice were stained with H&E to determine clinical severity of insulitis. Pancreatic islets were scored for the presence of mononuclear infiltration: 0, no infiltrate; 1, peri-insulitis present; 2, 25–50% of the islet contained infiltrate; 3, more than 50% of the islet was infiltrated. Average percentages shown were determined from at least 100 islets from at least 3 mice per group. (C) Flow cytometric analysis was performed to determine the percentage of CD4⁺CD25⁺CD62L⁺ and (D) CD4⁺CD25⁺FoxP3⁺ Tregs in the lymphoid tissue of NOD.B7 DKO, NOD. B7 DKO.scαCTLA-4 Tg⁺, and NOD mice. The mean ± SD from at least 3 mice per group is shown. Results shown are representative of 3 independent experiments.