Details

Autor(en) / Beteiligte

• 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
• Falkenburg, J H Frederik

Titel

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

Ist Teil von

• The Journal of clinical investigation, 2017-02, Vol.127 (2), p.517-529

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.