title: Antibody-mediated rejection of arterialised venous allografts is inhibited by immunosuppression in rats.
abstract: OBJECTIVE
  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.
  
  
  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% ± 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Splith
authors.affiliation: Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Fellmer
authors.affiliation: Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Ivan
authors.initials: I
authors.lastname: Matia
authors.affiliation: Transplant Surgery Department, Institute for Clinical und Experimental Medicine, Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Varga
authors.affiliation: Transplant Surgery Department, Institute for Clinical und Experimental Medicine, Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Oliverius
authors.affiliation: Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kuhn
authors.affiliation: Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany; Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Feldbrügge
authors.affiliation: Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Krenzien
authors.affiliation: Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Hans-Michael
authors.initials: HM
authors.lastname: Hau
authors.affiliation: Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Wiltberger
authors.affiliation: Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany; Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Schmelzle
authors.affiliation: Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany; Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Jonas
mesh_terms: D064591:Allografts / Q000276:immunology*; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects / Q000276:immunology*; D001158:Arteries / Q000637:transplantation*; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007165:Immunosuppression Therapy; D007518:Isoantibodies / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008297:Male; D051381:Rats; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014181:Transplantation Immunology; D014680:Veins / Q000276:immunology / Q000637:transplantation*
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies