Inhibition of immune cell infiltration and induction of active tolerance by the low-molecular-weight compound VAG539. (A) Diabetic Balb/c female mice received a transplant of pancreatic islets isolated from C57Bl/6 allogeneic donors and were treated orally with VAG539 from day 1 to day 30 after transplantation (at 30 or 7.5 mg/kg per day). Graft survival was monitored by weekly measurement of blood glucose level. (B) Balb/c recipient mice received a transplant of C57Bl/6 islets and were treated orally with saline or VAG539 (30 mg/kg per day). Ten days after transplantation, kidneys were extracted, cryosectioned at the transplant area, and stained for the indicated markers. Sections from treated mice display reduced infiltration of DCs and CD8+ T cells into the transplant area (bar represents 100 μm). (C) VAG539 (30 mg/kg)–treated and control mice with long-term graft survival, shown in panel A, were challenged with fresh donor-type splenocytes (3 × 107 intraperitoneally). Graft survival was monitored by measurement of blood glucose level (see also Table 1).
