In vivo Prevention of Transplant Arteriosclerosis by ex vivo Expanded Human Regulatory T Cells

Transplant arteriosclerosis (TA) is the hallmark of chronic allograft dysfunction (CAD) affecting transplanted organs in the long term [1,2]. These fibroproliferative lesions lead to neointimal thickening of arteries in all transplanted allografts [2]. Luminal narrowing then leads to graft ischemia and organ demise. To date, there are no known tolerance induction strategies that prevent TA [3,4]. Therefore, this study was designed to test the hypothesis that human regulatory T cells (T(reg) cells) expanded ex vivo could prevent TA. Here we show the comparative capacity of T(reg) cells, sorted via two separate strategies, to prevent TA in a clinically relevant chimeric humanized mouse system. We found that the in vivo development of TA in human arteries was prevented with the treatment of ex vivo expanded human T(reg) cells. Additionally, we show that T(reg) cells sorted based on the low expression of CD127 (IL-7Rα) provide a more potent therapy to conventional T(reg) cells. Our results demonstrate, for the first time, that human T(reg) cells can inhibit TA by impairing effector function and graft infiltration. We anticipate our findings to serve as a foundation for the clinical development of therapeutics targeting TA in both allograft transplantation and other immune-mediated causes of vasculopathy [5].