Research ArticleTransplantation

Human Regulatory T Cells with Alloantigen Specificity Are More Potent Inhibitors of Alloimmune Skin Graft Damage than Polyclonal Regulatory T Cells

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Science Translational Medicine  18 May 2011:
Vol. 3, Issue 83, pp. 83ra42
DOI: 10.1126/scitranslmed.3002076

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Slip Me Some Skin

It’s never easy being the new kid on the block. You have to both look and act correctly to fit in. Skin grafts have similar problems—if they don’t express the same molecules as the surrounding host tissue, they will be rejected by the recipient’s own immune system. In the clinic, the standard way to combat this rejection is through the use of immunosuppressive drugs that broadly stem the immune response. However, general immune suppression has its own problems, including increased susceptibility to infection and cancer. In an ideal clinical scenario, only those immune cells responsible for attacking the transplant would be suppressed. Now, Sagoo et al. have established a way to do just that.

Regulatory T cells (Tregs) can suppress specific types of immune activation; however, it is difficult to isolate Tregs restricted to particular antigens and then purify these cells in sufficient numbers to transfer into transplant recipients for targeted immune suppression. Sagoo et al. described a method to isolate such activated alloreactive Tregs, which specifically suppress effector immune cells that target antigens on donor tissue and cause rejection. These Tregs were sorted and expanded if they expressed two activation markers, CD69 and CD71, after allospecific activation in vitro. Transfer of these customized Tregs into a humanized mouse transplant model prevented transplant rejection and skin damage with higher efficacy than that associated with the transfer of nonspecific, polyclonal Tregs. This relatively simple isolation protocol should be translatable to the clinic and, thus, help skin transplants to “fit in.”

Footnotes

  • * These authors contributed equally to this work.

  • Citation: P. Sagoo, N. Ali, G. Garg, F. O. Nestle, R. I. Lechler, G. Lombardi, Human Regulatory T Cells with Alloantigen Specificity Are More Potent Inhibitors of Alloimmune Skin Graft Damage than Polyclonal Regulatory T Cells. Sci. Transl. Med. 3, 83ra42 (2011).

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