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
Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany.
Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Leipzig, Germany.
PLoS One. 2014 Mar 11;9(3):e91212. doi: 10.1371/journal.pone.0091212. eCollection 2014.
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.
我们在大鼠模型中确定了：（1）在他克莫司免疫抑制下，接受布朗 - 挪威髂腰静脉移植的刘易斯（LEW）受体血清中识别静止布朗 - 挪威（BN）脾细胞上MHC复合物的同种抗体的存在及动态变化；（2）急性排斥静脉同种异体移植物壁中免疫球蛋白的存在情况。
采用流式细胞术分析从接受同基因髂腰静脉移植（A组）或布朗 - 挪威移植（B组、C组）的刘易斯受体在第0天、第14天和第30天获得的血清中是否存在供体特异性抗MHC I类和II类抗体。从第1天至第30天每天给予他克莫司0.2mg/kg（C组）。在第30天进行组织学检查。
比较了所有组术前及第30天获得的血清。仅在同种异体未免疫抑制的B组中观察到抗MHC I类和II类抗体结合的统计学显著下降（脾细胞：MHC I类 - 第0天（93% ± 7%）对第30天（66% ± 7%），p = 0.02；MHC II类 - 第0天（105% ± 3%）对第30天（83% ± 5%），p = 0.003；B细胞：MHC I类 - 第0天（83% ± 5%）对第30天（55% ± 6%），p = 0.003；MHC II类 - 第0天（101% ± 1%）对第30天（79% ± 6%），p = 0.006；T细胞：MHC I类 - 第0天（71% ± 7%）对第30天（49% ± 5%），p = 0.04）。在任何实验组中均未检测到游离的免疫球蛋白G沉积簇。
动脉化静脉同种异体移植物诱导强烈的供体特异性抗MHC I类和抗MHC II类抗体产生，随后这些同种异体移植物发生免疫介导性破坏，且无免疫球蛋白G沉积证据。低剂量他克莫司可抑制供体特异性抗体产生。
