title: Immunosuppressive protocol with delayed use of low-dose tacrolimus after aortic transplantation suppresses donor-specific anti-MHC class I and class II antibody production in rats.
abstract: BACKGROUND
  Arterial allografts are used as vascular conduits in the treatment of prosthetic graft infection. Immunosuppression decreases their rupture risk rate. However, immunosuppression can be unprofitable in florid infection. Previously, we confirmed inhibition of cell-mediated destruction of rat aortic grafts by delayed use of tacrolimus. In this work, we studied the influence of this protocol on the antibody-mediated rejection.
  
  
  METHODS
  Flow cytometry was used for the retrospective analysis of day 0, 14, and 30 sera obtained from Lewis rat recipients of isogeneic fresh infrarenal aortic grafts (group A) or Brown-Norway rat aortic grafts (group B,C,D) for the presence of donor-specific anti-MHC class I and II antibodies. Tacrolimus in daily dose of 0.2 mg/kg was administered from day 1 to day 30 (group C) or from day 7 to day 30 (group D).
  
  
  RESULTS
  Inhibition of fluorescence-labeled anti-BN MHC class I and MHC class II antibodies binding to BN-splenocytes was observed only by day 14 and day 30 sera of allogeneic non-immunosuppressed Lewis rats (group B). The day 30 sera significantly decreased anti-MHC I (42±3%) and anti-MHC II antibody binding (56±3%) compared to day 0 (76±9%, p=0.005 and 79±5%, p=0.003, respectively). Deposition of immunoglobulins G into the tunica media was observed only in non-immunosuppressed aortic allografts on day 30.
  
  
  CONCLUSIONS
  Fresh aortic allografts induce donor-specific anti-MHC class I and anti-MHC class II antibody production. Delayed administration of tacrolimus completely suppressed antibody production and antibody-mediated destruction of aortic allografts.
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: Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Fellmer
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 Transplant Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Varga
authors.affiliation: Department of Transplant Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Milos
authors.initials: M
authors.lastname: Adamec
authors.affiliation: Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Kämmerer
authors.affiliation: 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: Georgi
authors.initials: G
authors.lastname: Atanasov
authors.affiliation: Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Schmelzle
authors.affiliation: Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Jonas
mesh_terms: D000818:Animals; D001011:Aorta / Q000637:transplantation*; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007518:Isoantibodies / Q000276:immunology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology*; D014184:Transplantation, Homologous; D058017:Vascular Grafting / Q000379:methods*
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D016559:Tacrolimus