Prévention du rejet d'allogreffe intestinale par des anticorps antimolécules d'adhésion dans un modèle murin

Abstract

Study aim Small bowel transplantation is still hampered by a high morbidity and mortality linked to the heavy non specific immunosuppression which is required by the transplantation of this lymphoid organ. Adhesion molecules appear to be potential targets for specific immunosuppression. The aim of the study was to investigate the effect of a transitory administration of anti-LFA-1 or anti-α4 monoclonal antibodies (mAb) in the prevention of rejection in a model of fetal small-bowel transplantation in mice. Materials and methods The small bowel of C57BL/6 (H-2 b) fetus (16 to 20 days of gestation) was transplanted into adult C3H/He mice (H-2 k) or C57BL/6 recipient mice. Recipients were treated with a short course of either antiLFA-1 mAb alone, either with anti-α4 mAb alone, or with both mAb. Biopsies with histological study of the grafts were performed between post-operative day 5 and 60. A score of development and rejection was assigned to each sample. Results Normal intestinal development with no sign of rejection was observed in 24/28 syngenic grafts till postoperative day 45. In the absence of treatment, intense rejection was observed as soon as day 5 and all allogenic grafts were rejected ( n=22). In contrast, in anti-LFA-1 mAb treated mice, 18/20 allogenic grafts developed normally with minimal signs of rejection. In anti-α4 treated mice, a transient protective effect on small bowel allograft survival was observed on day 7 but thereafter, all grafts were massively rejected within a few days ( n = 18). The combination of both mAb didn't improve the survival of the grafts when compared to anti-LFA-1 mAb treated grafts ( n = 10). Conclusion These results demonstrate that a transitory administration of anti-LFA-1 mAb, but not of anti-α4 mAb, is able to prolong significantly the survival of non vascularized small bowel fetal grafts in mice. Our results are promising for the possible use of the anti-LFA-1 mAb in clinical intestinal transplantation.