Antibody-Mediated Rejection of Arterialised Venous Allografts Is Inhibited by Immunosuppression in Rats

Objectives and Design: We determined in a rat model (1) the presence and dynamics of alloantibodies recognizing MHC complexes on quiescent Brown-Norway (BN) splenic cells in the sera of Lewis (LEW) recipients of Brown-Norway iliolumbar vein grafts under tacrolimus immunosuppression; and (2) the presence of immunoglobulins in the wall of acute rejected vein allografts. Materials and Methods: Flow cytometry was used for the analysis of day 0, 14 and 30 sera obtained from Lewis recipients of isogeneic iliolumbar vein grafts (group A) or Brown-Norway grafts (group B, C) for the presence of donor specific anti-MHC class I and II antibodies. Tacrolimus 0.2 mg/kg daily was administered from day 1 to day 30 (group C). Histology was performed on day 30. Results: Sera obtained preoperatively and on day 30 were compared in all groups. The statistically significant decrease of anti MHC class I and II antibody binding was observed only in allogenic non-immunosuppressed group B (splenocytes: MHC class I-day 0 (93%+/-67%) vs day 30 (66%+/-67%), p = 0.02, MHC class II-day 0 (105%+/-63%) vs day 30 (83%+/-65%), p = 0.003; B-cells: MHC class I-day 0 (83%+/-65%) vs day 30 (55%+/-66%), p = 0.003, MHC class II-day 0 (101%+/-61%) vs day 30 (79%+/-66%), p = 0.006; T-cells: MHC class I-day 0 (71%+/-67%) vs day 30 (49%+/-65%), p = 0.04). No free clusters of immunoglobulin G deposition were detected in any experimental group. Conclusion: Arterialized venous allografts induce strong donor-specific anti-MHC class I and anti-MHC class II antibody production with subsequent immune-mediated destruction of these allografts with no evidence of immunoglobulin G deposition. Low-dose tacrolimus suppress the donor-specific antibody production.