Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Biol Blood Marrow Transplant. 2020 Jul;26(7):1257-1265. doi: 10.1016/j.bbmt.2020.03.001. Epub 2020 Mar 10.
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，用供体干细胞移植物中的细胞替代患病的造血系统。大多数 10/10 配型的无关供体均存在 HLA-DP 错配，这可能导致移植物抗白血病（GVL）效应的程度不同，同时伴有或不伴有移植物抗宿主病（GVHD）。供体 T 细胞库中通常存在同种异体 HLA 反应性 T 细胞，因此在 HLA-DP 错配的情况下，可以引发非常强烈的同种异体反应性免疫反应。同种异体 HLA-DP 特异性免疫反应的幅度和多样性可能决定了移植后 GVL 和/或 GVHD 的发生平衡。为了了解在不同刺激条件下引发的同种异体 HLA-DP 特异性免疫反应的性质，我们使用 HLA-DP 错配的专业抗原呈递细胞（APCs）（单核细胞衍生的树突状细胞[allo-DC]）或 HLA-DP 错配的非专业 APC（皮肤衍生的成纤维细胞[allo-成纤维细胞]）从幼稚 T 细胞和记忆 T 细胞中诱导免疫反应。在这项研究中，我们观察到同种异体 HLA-DP 反应性 T 细胞可以通过这两种 APC 从幼稚和记忆细胞中被诱导出来。然而，用 allo-DC 进行刺激时，同种异体 HLA-DP 特异性免疫反应的幅度更大。此外，我们发现，与记忆 T 细胞相比，幼稚 T 细胞中同种异体 HLA-DP 反应性 T 细胞的频率更高，但观察到这些同种异体 HLA-DP 特异性反应具有相似的谱系特异性。总的来说，这项研究的数据表明，受体来源的专业 APC 的存在将主要决定从幼稚和记忆 T 细胞中诱导的同种异体 HLA-DP 特异性免疫反应的幅度，但不能单独介导这些免疫反应的诱导。
