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Updated: Aug 21, 2026
Murine Cervical Heart Transplantation Model Using a Modified Cuff Technique
Published on: October 12, 2014
Cardiac allograft vasculopathy is abrogated by anti-CD8 monoclonal antibody therapy
1Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Insights
Depleting CD8+ T cells in swine prevented intimal proliferation, a key feature of cardiac allograft vasculopathy. This highlights the role of CD8+ lymphocytes in early graft disease development.
Area of Science:
- Immunology
- Cardiology
- Transplantation
Background:
- Cardiac allograft vasculopathy (CAV) is a major cause of graft loss and death after heart transplantation.
- CAV is characterized by accelerated arteriosclerosis in the transplanted heart graft.
- This study investigated the role of CD8+ T lymphocytes in CAV development.
Purpose of the Study:
- To examine the effect of depleting host CD8+ T lymphocytes on CAV development in a miniature swine model.
- To understand the contribution of CD8+ T cells to the early stages of cardiac allograft vasculopathy.
Main Methods:
- Miniature swine underwent heterotopic cardiac transplantation across a MHC class I barrier.
- Animals received either cyclosporine alone (control) or cyclosporine plus a CD8-depleting monoclonal antibody (76-2-11).
- Graft rejection was monitored via biopsies, ECGs, and echocardiograms; CD8+ T cell depletion was confirmed by flow cytometry.
Main Results:
- CD8+ T cell depletion was achieved and persisted for 14-18 days post-transplant.
- While mean allograft survival was similar between groups, CD8-depleted animals showed no intimal proliferation.
- Control animals exhibited severe intimal thickening in graft arteries, whereas CD8-depleted animals did not.
Conclusions:
- Depletion of host CD8+ T cells effectively prevents intimal proliferation in this swine model.
- CD8+ lymphocytes play a critical role in the early development of cardiac allograft vasculopathy.
- Targeting CD8+ T cells may offer a therapeutic strategy to prevent or delay CAV.
Background:
Cardiac allograft vasculopathy, a diffuse and accelerated form of arteriosclerosis, is a major cause of graft loss or heart transplant recipient death after the first transplant year. This study examined the effects of depleting host CD8 + T lymphocytes on the development of cardiac allograft vasculopathy in miniature swine.
Methods:
Cardiac allografts were heterotopically transplanted across a major histocompatibility complex class I barrier in partially inbred miniature swine and monitored for rejection by serial biopsies, electrocardiograms, and echocardiograms. Four control animals received cyclosporine on postoperative days 0 to 11. Another four miniswine were given 14.5 mg/kg of 76-2-11 (a mouse anti-swine CD8 monoclonal antibody) on postoperative day 0, in addition to a 12-day course of cyclosporine. Host CD8+ T cells and circulating 76-2-11 monoclonal antibodies were monitored by flow cytometry.
Results:
As compared with cyclosporine-treated control animals, swine receiving 76-2-11 demonstrated near-complete depletion of peripheral CD8+ T cells by postoperative day 2, which persisted for 14 to 18 days. Mean allograft survival of the antibody-treated group and the control group was not statistically different (33 days versus 39 days, respectively) and both groups demonstrated severe interstitial rejection at necropsy. Control animals demonstrated florid intimal thickening of large and small arteries at necropsy. However, swine treated with 76-2-11 showed no intimal proliferation.
Conclusions:
Depletion of host CD8+ T cells prevents or delays the development of intimal proliferation in miniature swine. CD8+ lymphocytes play an important role in the early development of cardiac allograft vasculopathy in large animals.
