Frequent HLA-DR loss on hematopoietic stem progenitor cells in patients with cyclosporine-dependent aplastic anemia carrying HLA-DR15
Frequent HLA-DR loss on hematopoietic stem progenitor cells in patients with cyclosporine-dependent aplastic anemia carrying HLA-DR15
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携带 HLA-DR15 的环孢素依赖性再生障碍性贫血患者的造血干祖细胞频繁出现 HLA-DR 丢失
DOI：
10.1038/s41375-022-01549-6
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发表时间：
2022
期刊：
影响因子：
11.4
通讯作者：
Nakao Shinji
中科院分区：
文献类型：
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作者：
Tsuji Noriaki;Hosokawa Kohei;Urushihara Ryota;Tanabe Mikoto;Katagiri Takamasa;Ozawa Tatsuhiko;Takamatsu Hiroyuki;Ishiyama Ken;Yamazaki Hirohito;Kishi Hiroyuki;Ogawa Seishi;Nakao Shinji
为了确定造血干祖细胞（HSPCs）上HLA-DR的抗原呈递是否参与了获得性再生障碍性贫血（AA）的发生，我们研究了61例AA患者外周血中CD 45 dimCD 34 + CD 38+细胞上HLA-DR的表达，其中包括23例HLA-I类等位基因缺乏（HLA-I [-]）的患者。在7例（11.5%）HLA-DR 15患者中，HLA-DR缺乏（DR[−]）细胞占总HSPC的13.0-57.1%，这些患者不具有HLA-I（-）类白细胞。分选的DR（-）HSPC在IFN-γ存在下孵育72小时导致DR表达的完全恢复。DR（-）和DR（+）HSPC之间的转录组谱的比较揭示了免疫应答相关基因的较低表达，包括共刺激分子（例如，CD 48、CD 74和CD 86），这在HLA I类（-）HSPC中不明显。DR（-）细胞仅在4名患者的GPI（+）HSPC中检测到，这些患者的HSPC可以分别分析GPI（+）和GPI（-）HSPC。这些发现表明，对HSPC上HLA-DR 15呈递的抗原具有特异性的CD 4 +T细胞可能以与识别HLA-I类限制性抗原的CD 8 +T细胞不同的方式促进AA的发生以及GPI（-）HSPC的免疫逃逸。
To determine whether antigen presentation by HLA-DR on hematopoietic stem progenitor cells (HSPCs) is involved in the development of acquired aplastic anemia (AA), we studied the HLA-DR expression on CD45dimCD34+CD38+cells in the peripheral blood of 61 AA patients including 23 patients possessing HLA-class I allele-lacking (HLA-class I[−]) leukocytes. HLA-DR-lacking (DR[−]) cells accounted for 13.0–57.1% of the total HSPCs in seven (11.5%) patients with HLA-DR15 who did not possess HLA-class I(–) leukocytes. The incubation of sorted DR(–) HSPCs in the presence of IFN-γ for 72 h resulted in the full restoration of the DR expression. A comparison of the transcriptome profile between DR(–) and DR(+) HSPCs revealed the lower expression of immune response-related genes including co-stimulatory molecules (e.g., CD48, CD74, and CD86) in DR(–) cells, which was not evident in HLA-class I(–) HSPCs. DR(–) cells were exclusively detected in GPI(+) HSPCs in four patients whose HSPCs could be analyzed separately for GPI(+) and GPI(–) HSPCs. These findings suggest that CD4+T cells specific to antigens presented by HLA-DR15 on HSPCs may contribute to the development of AA as well as the immune escape of GPI(–) HSPCs in a distinct way from CD8+T cells recognizing HLA-class I-restricted antigens.