[The effects of NKG2D mAb on the survival of allogeneic transplanted islets in spontaneous diabetic nonobese diabetic mice].

OBJECTIVE

To investigate the effects of NKG2D mAb on the survival of allogeneic transplanted islets nonobese diabetic (NOD) mice, and to find if CD154 mAb has synergistic effects.

METHODS

Spontaneous diabetic NOD mice transplanted with allogeneic islets of BALB/c mice were divided into 4 groups. Group A was control group, Group B were treated with anti-NKG2D monoclonal antibody (mAb), Group C were treated with CD154 mAb (MR1), Group D were treated with NKG2D mAb and MR1. Glucose levels were monitored at regular intervals through caudal vein, and islet function was evaluated by glycemia. Histological study was performed at graft rejection or at day 120. Spleen cell suspension was prepared for mixed lymphocyte cultivation. The kidneys hosting the islet graft were prepared with HE staining and immuno-histochemistry staining of CD3, CD4 and CD8 was performed.

RESULTS

MR1 therapy alone significantly prolonged the survival of islet grafts when compared to NKG2D mAb group and the control group: median graft survival was 41 days versus 8 days (P < 0.05) and 8 days (P < 0.05), respectively. Combination therapy with NKG2D mAb and MR1 prolonged islet grafts survival when compared to MR1 therapy alone: median graft survival was 51 days versus 41 days (P > 0.05).

CONCLUSION

NKG2D mAb alone did not result in the prolongation of islet graft survival, whereas CD154 mAb increased graft survival. When both antibodies were administered, a synergistic effect was obtained, but did not provide permanent protection from diabetes recurrence.