Antibody-mediated rejection of arterialised venous allografts is inhibited by immunosuppression in rats

• Published in: PloS one 2014-03, Vol.9 (3), p.e91212-e91212
• Main Authors: Splith, Katrin, Fellmer, Peter, Matia, Ivan, Varga, Martin, Oliverius, Martin, Kuhn, Stephanie, Feldbrügge, Linda, Krenzien, Felix, Hau, Hans-Michael, Wiltberger, Georg, Schmelzle, Moritz, Jonas, Sven
• Format: Article
• Language: English
• Subjects: Allografts - immunology; Animals; Antibody-Dependent Cell Cytotoxicity - drug effects; Antibody-Dependent Cell Cytotoxicity - immunology; Antigens; Arteries - transplantation; Biology; Coronary vessels; Drug dosages; Graft Rejection - drug therapy; Graft Rejection - immunology; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - metabolism; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; Homografts; Immunoglobulin G; Immunoglobulins; Immunosuppression; Immunotherapy; Isoantibodies - immunology; Laboratory animals; Lymphocyte Subsets - immunology; Lymphocyte Subsets - metabolism; Male; Medical research; Medicine; MHC antibodies; Rats; Rodents; Spleen - cytology; Spleen - immunology; Spleen - metabolism; T cells; Tacrolimus; Thrombosis; Time Factors; Transplantation Immunology; Transplants & implants; Vascular surgery; Veins & arteries; Veins - immunology; Veins - transplantation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0091212

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. 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. 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% ± 7% ) vs day 30 (66% ± 7%), p = 0.02, MHC class II - day 0 (105% ± 3% ) vs day 30 (83% ± 5%), p = 0.003; B-cells: MHC class I - day 0 (83% ± 5%) vs day 30 (55% ± 6%), p = 0.003, MHC class II - day 0 (101% ± 1%) vs day 30 (79% ± 6%), p = 0.006; T-cells: MHC class I - day 0 (71% ± 7%) vs day 30 (49% ± 5%), p = 0.04). No free clusters of immunoglobulin G deposition were detected in any experimental group. 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.