[Prevention of intestinal allograft rejection by anti-adhesion molecule antibodies in a mouse model].
OBJECTIVE
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-alpha 4 monoclonal antibodies (mAb) in the prevention of rejection in a model of fetal small-bowel transplantation in mice.


METHODS
The small bowel of C57BL/6 (H-2b) fetus (16 to 20 days of gestation) was transplanted into adult C3H/He mice (H-2k) or C57BL/6 recipient mice. Recipients were treated with a short course of either anti-LFA-1 mAb alone, either with anti-alpha 4 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 post-operative 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-alpha 4 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).


CONCLUSIONS
These results demonstrate that a transitory administration of anti-LFA-1 mAb, but not of anti-alpha 4 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.
Auber
F
F
Service de chirurgie pédiatrique, hôpital et faculté de médecine Necker-Enfants-Malades, Paris, France.
Cerf-Bensussan
N
N
Cavazzana-Calvo
M
M
Fauveau
V
V
Brousse
N
N
Fischer
A
A
Révillon
Y
Y
Sarnacki
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D005260:Female; D016332:Fetal Tissue Transplantation / Q000276:immunology* / Q000473:pathology; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules