TY - JOUR AU - van Bergen, Cornelis A.M. AU - van Luxemburg-Heijs, Simone A.P. AU - de Wreede, Liesbeth C. AU - Eefting, Matthijs AU - von dem Borne, Peter A. AU - van Balen, Peter AU - Heemskerk, Mirjam H.M. AU - Mulder, Arend AU - Claas, Fransiscus H.J. AU - Navarrete, Marcelo A. AU - Honders, Wilhelmina M. AU - Rutten, Caroline E. AU - Veelken, Hendrik AU - Jedema, Inge AU - Halkes, Constantijn J.M. AU - Griffioen, Marieke AU - Falkenburg, J.H. Frederik T1 - Selective graft-versus-leukemia depends on magnitude and diversity of the alloreactive T cell response PY - 2017/02/01/ AB - Patients with leukemia who receive a T cell–depleted allogeneic stem cell graft followed by postponed donor lymphocyte infusion (DLI) can experience graft-versus-leukemia (GVL) reactivity, with a lower risk of graft-versus-host disease (GVHD). Here, we have investigated the magnitude, diversity, and specificity of alloreactive CD8 T cells in patients who developed GVL reactivity after DLI in the absence or presence of GVHD. We observed a lower magnitude and diversity of CD8 T cells for minor histocompatibility antigens (MiHAs) in patients with selective GVL reactivity without GVHD. Furthermore, we demonstrated that MiHA-specific T cell clones from patients with selective GVL reactivity showed lower reactivity against nonhematopoietic cells, even when pretreated with inflammatory cytokines. Expression analysis of MiHA-encoding genes showed that similar types of antigens were recognized in both patient groups, but in patients who developed GVHD, T cell reactivity was skewed to target broadly expressed MiHAs. As an inflammatory environment can render nonhematopoietic cells susceptible to T cell recognition, prevention of such circumstances favors induction of selective GVL reactivity without development of GVHD. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI86175 VL - 127 IS - 2 UR - https://doi.org/10.1172/JCI86175 SP - 517 EP - 529 PB - The American Society for Clinical Investigation ER -