Figure 5. Involvement of CD40-CD40L interaction in production of IL-12 and IFN-γ in early loss of transplanted islets.

(A) CD40 expression in DCs and Neu before or after treatment with HMGB1. Liver MNCs (2 × 10⁶) were treated without or with HMGB1 (20 μg/ml) for 24 hours and analyzed for CD40 expression (n = 3). (B) Requirement of CD40-CD40L interaction in the production of IL-12 and IFN-γ in the presence of NKT cells. DCs or Neu (4 × 10⁴) were cocultured in vitro with NKT cells (2 × 10⁵) in the presence of HMGB1 (20 μg/ml) for 48 hours with or without addition of anti-CD40L antibody. IL-12 and IFN-γ levels were measured by CBA (n = 3). The values are expressed as the mean ± SD. *P < 0.05; **P < 0.01. (C) Nonfasting plasma glucose levels of STZ-induced diabetic mice that had received 200 syngeneic islets and were treated with control goat IgG or goat anti-mouse IL-12 antibody and those with control hamster IgG or hamster anti-mouse CD40L antibody with 200 μg intraperitoneal injection per mouse at the time of transplantation. Individual lines represent the nonfasting plasma glucose levels of each diabetic mouse after islet transplantation.