Department of Clinical Immunology, Odense University Hospital and Clinical Institute, University of Southern Denmark, Odense, Denmark.
PLoS One. 2013;8(1):e54366. doi: 10.1371/journal.pone.0054366. Epub 2013 Jan 18.
A major problem of allogeneic stem cell therapy is immunologically mediated graft rejection. HLA class I A, B, and Cw antigens are crucial factors, but little is known of their respective expression on stem cells and their progenies. We have recently shown that locus-specific expression (HLA-A, but not -B) is seen on some multipotent stem cells, and this raises the question how this is in other stem cells and how it changes during differentiation. In this study, we have used flow cytometry to investigate the cell surface expression of HLA-A and -B on human embryonic stem cells (hESC), human hematopoietic stem cells (hHSC), human mesenchymal stem cells (hMSC) and their fully-differentiated progenies such as lymphocytes, adipocytes and osteoblasts. hESC showed extremely low levels of HLA-A and no -B. In contrast, multipotent hMSC and hHSC generally expressed higher levels of HLA-A and clearly HLA-B though at lower levels. IFNγ induced HLA-A to very high levels on both hESC and hMSC and HLA-B on hMSC. Even on hESC, a low expression of HLA-B was achieved. Differentiation of hMSC to osteoblasts downregulated HLA-A expression (P = 0.017). Interestingly HLA class I on T lymphocytes differed between different compartments. Mature bone marrow CD4(+) and CD8(+) T cells expressed similar HLA-A and -B levels as hHSC, while in the peripheral blood they expressed significantly more HLA-B7 (P = 0.0007 and P = 0.004 for CD4(+) and CD8(+) T cells, respectively). Thus different HLA loci are differentially regulated during differentiation of stem cells.
同种异体干细胞治疗的一个主要问题是免疫介导的移植物排斥。HLA Ⅰ类 A、B 和 Cw 抗原是至关重要的因素，但它们在干细胞及其后代上的各自表达知之甚少。我们最近表明，一些多能干细胞上存在特异性表达（HLA-A，但不是-B），这就提出了一个问题，即在其他干细胞中情况如何，以及在分化过程中如何变化。在这项研究中，我们使用流式细胞术研究了人类胚胎干细胞（hESC）、人类造血干细胞（hHSC）、人类间充质干细胞（hMSC）及其完全分化的后代（如淋巴细胞、脂肪细胞和成骨细胞）表面 HLA-A 和 -B 的表达。hESC 显示 HLA-A 极低水平，而没有-B。相比之下，多能 hMSC 和 hHSC 通常表达更高水平的 HLA-A，并且明显 HLA-B，尽管水平较低。IFNγ诱导 hESC 和 hMSC 上的 HLA-A 非常高水平，以及 hMSC 上的 HLA-B。即使在 hESC 上，也能达到 HLA-B 的低表达水平。hMSC 向成骨细胞分化下调 HLA-A 表达（P = 0.017）。有趣的是，不同隔间之间 T 淋巴细胞上的 HLA Ⅰ类存在差异。成熟骨髓 CD4(+)和 CD8(+)T 细胞表达与 hHSC 相似的 HLA-A 和 -B 水平，而在外周血中，它们表达明显更多的 HLA-B7（CD4(+)和 CD8(+)T 细胞分别为 P = 0.0007 和 P = 0.004）。因此，在干细胞分化过程中，不同的 HLA 基因座受到不同的调节。
