Priming of allo-HLA-DP-specific reactivity from the naïve T-cell compartment is not exclusively mediated by professional antigen presenting cells

Abstract Allogeneic stem cell transplantation is applied to patients suffering from hematological malignancies to replace the diseased hematopoietic system with cells derived from a donor stem cell graft. The majority of 10/10 matched unrelated donors are HLA-DP-mismatched and this may result in varying degrees of graft-versus-leukemia (GVL) effect with or without the occurrence of graft-versus-host disease (GVHD). Allo-HLA-reactive T cells are commonly present in the donor T-cell repertoire and therefore a very profound allo-reactive immune response can be provoked in the HLA-DP-mismatched setting. The magnitude and the diversity of the allo-HLA-DP-specific immune response likely dictates the balance between the occurrence of GVL and/or GVHD after transplantation. To understand the nature of the allo-HLA-DP-specific immune response provoked under different stimulatory conditions, immune responses were induced from both the naive and memory T-cell compartment using either HLA-DP-mismatched professional (monocyte-derived dendritic cells, alloDC) or HLA-DP-mismatched non-professional APC (skin-derived fibroblasts, alloFibroblasts) as stimulator cells. In this study we observed that allo-HLA-DP-reactive T cells could be provoked from both the naive and memory compartment by both types of APC. However, the magnitude of the allo-HLA-DP-specific immune response was greater when stimulation was performed with alloDC. Moreover, we found that the frequency of allo-HLA-DP-reactive T cells was greater in the naive T-cell compartment compared to the memory T-cell compartment, but we observed a comparable lineage specificity of these allo-HLA-DP-specific reactivities. Overall, the data in this study illustrate that the presence of professional APC of recipient origin will mostly dictate the magnitude of the allo-HLA-DP-specific immune response derived from both the naive and memory T-cell compartment, but does not exclusively mediate the induction of these immune responses.