The pathogenic role of terminally differentiated effector memory (TEMRA) CD8+T cells has been implicated in kidney transplant failure. The authors showed that humoral rejection of kidney allografts is associated with an accumulation of cytolytic TEMRA CD8+T cells in blood and in kidney graft biopsies. They demonstrated that TEMRA CD8+T cells from kidney transplant recipients exhibit enhanced migratory properties compared with effector memory CD8+T cells and that the chemokine CXCL12 not only promotes migration of TEMRA CD8+T cells toward nonlymphoid organs but also triggers a purinergic P2X4 receptor–dependent proinflammatory response. They also found that agents aimed at potential TEMRA CD8+T cell–specific targets inhibited the migration of TEMRA CD8+T cells from kidney transplant recipients, suggesting a possible strategy in treating kidney transplant failure.