Aim: Study the preventive effect of a non-depleting monoclonal antibody specific for the LFA-1 a chain (CD11a) on the rejection of vascularized cardiac and skin grafts in the same haplotype disparate mouse strain combination.
Subjects: Male C57B6/DBA2 (H2b d) and C3H/DBA2 (H2k/d) mice were used respectively as donors and recipients.
Interventions: Fully vascularized heterotopic heart transplantation was performed using microsurgical techniques. Full-thickness tail were grafted onto the lateral thoracic wall of recipient mice. Anti-LFA-1(α subunit, rat IgG2a) was administered to recipients on day-1,0,1,4,6,8 and 11 with a total dose of 0,7mg. In long-term surviving heart allografted mice, on day 60, syngeneic, donor and third party (H2s) skin graft were performed.
Results: anti-LFA-1 antibody treatment had no effect on the prolongation of skin graft survival but significantly prolonged the survival of cardiac allografts (70 days versus 11 days in untreated recipients) In mice which tolerated their cardiac graft for more than 70 days, there was a slight delay in the rejection of donor skin graft but no in vitro (MLR and CTL) evidence of tolerance.
Conclusion: These results indicate that a non-depleting anti-LFA-1 antibody, can efficiently protect against rejection of MHC-incompatible heart grafts. A similar study using monoclonal antibodies directed against LFA-1 and other members of the integrin family is under investigation in a model of small-bowel transplantation in mice.
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Sarnacki, S., Cavazzana-Calvo, M., Calise, D. et al. Promotion of mice cardiac allograft survival by transitory administration of LFA-1 antibody. 216. Pediatr Res 40, 551 (1996). https://doi.org/10.1203/00006450-199609000-00239