Using T Cells to Help Transplants ‘Fit In’

T cells
This image shows human regulatory T cells (green) interacting with immune antigen presenting cells (red) of human skin transplants performed in the humanized mouse, allowing the in vivo study of the biology and function of Treg therapy in preparation for clinical use. [Image courtesy of Dr. Pervinder Sagoo]

Three new mouse studies show that regulatory T cells can help skin transplants “fit in” to recipient tissue. Regulatory T cells are an important “self-check” built into the immune system to prevent excessive immune cell reactions. Scientists have been trying to harness the self-checking ability of regulatory T cells in the lab to prevent organ rejection in transplant patients. Currently, almost all transplant patients take immunosuppressive drugs to help combat immediate organ rejection.

Although these drugs work pretty well in the short term, they are unable to protect the patient from long-term rejection five or 10 years down the road. And because these drugs also suppress the healthy part of the immune system, they can lead to infection and other undesirable side effects. The body doesn’t normally make enough regulatory T cells to fend off transplant rejection, but by producing massive amounts of regulatory T cells in the lab and putting them back into patients, researchers hope to keep the immune system in check after transplantation.

Pervinder Sagoo and colleagues have figured out a way to use regulatory T cells to suppress only those immune cells responsible for attacking skin transplants. By taking cells from healthy mice and exposing them to cells from transplanted tissue in the lab, the team discovered markers that allowed them to pluck out “donor specific” T cells. The researchers next produced large amounts of these T cells in the lab and put them into mice with human transplanted skin grafts. The donor specific cells blocked only the type of immune response that causes transplant rejection.

Similarly, Andrew Bushell and colleagues produced donor specific regulatory T cells in the lab by a different method. The researchers found that inhibiting an enzyme called PDE3, using a drug called cilostamide (already used to treat vascular disease), can boost production of donor specific regulatory T cells and prevent skin transplant rejection in mice. In a third study, Bruce Blazer and colleagues describe another way to boost production of regulatory T cells in the lab—this time by using blood. Siphoning an initial supply of regulatory T cells from blood, the team used artificial antigen presenting cells to boost regulatory T cells up to 50 million times the original amount. When injected into mice, the regulatory T cells retained their immune suppressor function and protected the animals from succumbing tograft-versus-host disease. A related Perspective discusses how the push to produce and customize regulatory T cells could revolutionize organ transplantation and treatment of autoimmune diseases.

This research appears in the 18 May 2011 issue of Science Translational Medicine.

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