Donor T-cell exhaustion is considered a major mechanisms of tolerance induction after HSCT. Alloreactive T cells gradually progress to exhaustion after HSCT and lose their ability to induce graft-versus-leukemia (GVL) effect and GVHD over time. CNIs inhibit T cells to reach terminal exhaustion, leaving them in a transitory exhaustion state, thus limiting tolerance induction. Alloreactivity of transitory exhausted T cells can still be restored.