HLA-DP specific responses in allogeneic stem cell transplantation

Abstract

Clinical studies demonstrated that HLA-DPB1 mismatched stem cell transplantation (SCT) is associated with a decreased risk of disease relapse and an increased risk of graft versus host disease (GVHD) compared to HLA-DPB1 matched SCT. In T-cell depleted SCT, mismatching of HLA-DPB1 was not associated with an increased risk of severe GVHD, whereas a significant decreased risk of disease relapse was still observed. In this thesis we showed that HLA-DPB1 mismatched allo-SCT followed by donor lymphocyte infusion (DLI) late after transplantation can result in selective graft versus leukemia (GVL) reactivity. Although several studies have suggested that some HLA-DPB1-mismatches were less immunogenic, we demonstrated that all HLA-DPB1-mismatches as defined by allele typing are immunogenic and resulted in vitro in high frequency immune responses. Finally, in a cohort of 24 patients transplanted for various hematological ma lignancies with a 10 out 10 matched HLA-DPB1 mismatched SCT followed by DLI, HLA-DP specific immune responses were frequently found. The presence of HLA-DP specific CD4+ T cells correlated with clinical immune responses including both selective GVL-reactivity and GVHD. It is likely that in each individual local environmental circumstances possibly in combination with the induction of other immune responses may finally determine the balance between GVHD and GVL-reactivity HLA-DP HLA-class II mismatch alloreactivity hematopoietic stem cell transplantation donor lymphocyte infusion graft versus host disease graft versus leukemia reactivity immunotherapy