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Am J Transplant. 2009 Dec;9(12):2736-44. doi: 10.1111/j.1600-6143.2009.02847.x. Epub 2009 Oct 21.

Regulatory T-cell counter-regulation by innate immunity is a barrier to transplantation tolerance.

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  • 1Division of Surgery, Department of Transplantation, Massachusetts General Hospital, Boston, MA, USA.


Innate immune signals foster adaptive immunity through activation of antigen-presenting cells. Recent in vitro evidence suggests that innate signaling may also contribute to immunity by countering the effects of regulatory T cells (T-regs), counter-regulation. We present in vivo evidence using a transgenic skin allograft model that the function of T-regs is lost in the setting of acute skin transplantation but remains intact when grafts were transplanted 1 month prior to allow surgery-induced inflammation to abate. Our findings identify T-reg counter-regulation as a naturally occurring process that accompanies transplantation and an important barrier to T-reg-mediated tolerance. Our finding further highlights the central role of regulatory cell deactivation in the initiation of the immune response.

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