Session Name: B-cell / Antibody /Autoimmunity
Session Date & Time: None. Available on demand.
*Purpose: Cardiac allograft vasculopathy (CAV) is a major long-term complication of heart transplantation and the presence of donor specific antibodies (DSA) is associated with an increased incidence of CAV in heart transplant recipients. However, mechanisms underlying development and progression of the pathology remain poorly understood. We previously have reported that MHC-mismatched A/J cardiac allografts in B6.CCR5-/- recipients were acutely rejected within 7-10 days with low T cell infiltration, but intense deposition of C4d in the large vessels and capillaries of the graft, as well as high serum titers of DSA, characteristics observed in antibody-mediated rejection (AMR).
*Methods: In this study, we utilized this AMR model to investigate mechanisms of CAV development within the grafts. To test this, we transplanted A/J allografts into B6.CCR5-/- CD8 -/- mice and treated recipients with a low dose of anti-CD4 mAb on days 0, 2 and 7.
*Results: While the mild inhibition of CD4 T cells extended the survival of allografts, the grafts developed CAV with intense C4d deposition in the myocardial capillaries accompanied by macrophage infiltration on days 14 post-transplant. Consistent with this, DSA titers were also much higher than in B6.CD8-/- recipients. Interestingly, development of CAV was absent in semi-allogeneic (A/J x B6) F1 grafts which inhibit recipient NK cell activity.
*Conclusions: In conclusion, we have developed a novel antibody mediated CAV model using CCR5-/- CD8-/- mice as allograft recipients that will facilitate an understanding of molecular and cellular mechanisms of CAV.
To cite this abstract in AMA style:Tsuda H, Reed E, Baldwin W, Fairchild R. A Novel Mouse Model of Cardiac Allograft Vasculopathy [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/a-novel-mouse-model-of-cardiac-allograft-vasculopathy/. Accessed June 13, 2021.
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