1. Selective graft-versus-leukemia depends on magnitude and diversity of the alloreactive T cell response
- Author
-
van Bergen, Cornelis A.M., van Luxemburg-Heijs, Simone A.P., de Wreede, Liesbeth C., Eefting, Matthijs, von dem Borne, Peter A., van Balen, Peter, Heemskerk, Mirjam H.M., Mulder, Arend, Claas, Fransiscus H.J., Navarrete, Marcelo A., Honders, Wilhelmina M., Rutten, Caroline E., Veelken, Hendrik, Jedema, Inge, Halkes, Constantijn J.M., Griffioen, Marieke, and Falkenburg, J.H. Frederik
- Subjects
T cells -- Health aspects ,Leukemia -- Care and treatment -- Development and progression ,Immune response -- Regulation ,Stem cells -- Transplantation ,Health care industry - Abstract
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., Introduction The curative effect of allogeneic stem cell transplantation (allo-SCT) as a treatment modality for hematological malignancies is based on the capacity of donor T cells to effectively induce graft-versus-leukemia [...]
- Published
- 2017
- Full Text
- View/download PDF