Priming of Allo-HLA-DP-Specific Reactivity from the Naïve T Cell Compartment Is Not Exclusively Mediated by Professional Antigen-Presenting Cells.

Abstract

Allogeneic (allo) stem cell transplantation is applied to patients suffering from hematologic 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 the 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 thus a very profound alloreactive 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 naïve and memory T cell compartments using either HLA-DP-mismatched professional antigen-presenting cells (APCs) (monocyte-derived dendritic cells [allo-DCs]) or HLA-DP-mismatched nonprofessional APCs (skin-derived fibroblasts [allo-fibroblasts]) as stimulator cells. In this study, we observed that allo-HLA-DP-reactive T cells could be provoked from both the naïve and memory compartments by both types of APCs. However, the magnitude of the allo-HLA-DP-specific immune response was greater when stimulation was performed with allo-DCs. Moreover, we found that the frequency of allo-HLA-DP-reactive T cells was greater in the naïve T cell compartment compared with the memory T cell compartment, but we observed a comparable lineage specificity of these allo-HLA-DP-specific reactivities. Overall, the data from this study illustrate that the presence of professional APCs of recipient origin will mostly dictate the magnitude of the allo-HLA-DP-specific immune response derived from both the naïve and memory T cell compartments, but does not exclusively mediate the induction of these immune responses.