Activated CD4+ T cells expressing high levels of IL-7R (orange) infiltrate transplants.

Unlike grafts that are rejected immediately, those that fail gradually are thought to be rejected in part by CD4⁺ T cells. But activated CD4⁺ T cells are difficult to distinguish from the regulatory T (T reg) cells that suppress rejection, as both express CD4 and CD25. Only the T reg cells also express the transcription factor FOXP3, but their sparse numbers are difficult to follow in vivo. FOXP3⁺ cells express much less IL-7R than do other CD4⁺ T cells. So the team wondered whether IL-7R would be a convenient marker to follow activated T cells that enter the grafts.

They now find that CD4⁺ CD25⁺ cells expressing high levels of IL-7R are abundant in transplant patients. These cells infiltrated the grafts and were able to kill donor cells in vitro. Patients with delayed graft rejection had twice as many of these cells as did stable transplant recipients. Both groups had equal numbers of T reg cells, suggesting that graft rejection is caused by the increased numbers of activated T cells. The authors are now looking at patients to determine whether increases in IL-7R–expressing cells can be used to predict transplant rejection.

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