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.

同种异体（allo）干细胞移植应用于患有血液系统恶性肿瘤的患者，用来自供体干细胞移植物的细胞替代患病的造血系统。大多数10/10匹配的无关供体都是HLA-DP不匹配的，无论是否发生移植物抗宿主病（GVHD），这都可能导致不同程度的移植物抗白血病（GVL）效应。异体-HLA反应性T细胞通常存在于供体T细胞库中，因此，在HLA-DP不匹配的情况下，可以引发非常深刻的异体反应性免疫反应。异源HLA-DP特异性免疫应答的强度和多样性可能决定了移植后GVL和/或GVHD的发生之间的平衡。为了了解在不同刺激条件下引发的同种HLA-DP特异性免疫反应的性质，使用HLA-DP不匹配的专业抗原呈递细胞（APC）从幼稚和记忆T细胞区室诱导免疫反应（单核细胞来源的树突状细胞[allo-DCs]或HLA-DP不匹配的非专业APCs（皮肤来源的成纤维细胞[allo-fibroblasts]）作为刺激细胞。在这项研究中，我们观察到两种类型的APC均可从幼稚和记忆区中激发同种HLA-DP反应性T细胞。然而，当用allo-DC进行刺激时，allo-HLA-DP特异性免疫反应的强度更大。此外，我们发现，与记忆T细胞隔室相比，幼稚T细胞隔室中同种HLA-DP反应性T细胞的频率更高，但我们观察到这些allo-HLA-DP特异性反应性具有可比的谱系特异性。总体而言，这项研究的数据表明，受者来源的专业APC的存在将主要决定源自幼稚和记忆T细胞区室的同种HLA-DP特异性免疫反应的程度，但并不专门介导这种作用。这些免疫反应的诱导。