Selective graft-versus-leukemia depends on magnitude and diversity of the alloreactive T cell response.

Authors: van Bergen, Cornelis A M and van Luxemburg-Heijs, Simone A P and de Wreede, Liesbeth C and Eefting, Matthijs and von dem Borne, Peter A and van Balen, Peter and Heemskerk, Mirjam H M and Mulder, Arend and Claas, Fransiscus H J and Navarrete, Marcelo A and Honders, Wilhelmina M and Rutten, Caroline E and Veelken, Hendrik and Jedema, Inge and Halkes, Constantijn J M and Griffioen, Marieke and Falkenburg, J H Frederik

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.

Journal: The Journal of clinical investigation
DOI: 10.1172/JCI86175
Year: 2017

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