GPI-anchored protein-deficient T cells in patients with aplastic anemia and low-risk myelodysplastic syndrome: implications for the immunopathophysiology of bone marrow failure
GPI-anchored protein-deficient T cells in patients with aplastic anemia and low-risk myelodysplastic syndrome: implications for the immunopathophysiology of bone marrow failure
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DOI：
10.1111/j.1600-0609.2010.01563.x
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发表时间：
2011-03-01
影响因子：
3.1
通讯作者：
Nakao, Shinji
中科院分区：
文献类型：
--
作者：
Katagiri, Takamasa;Qi, Zhirong;Nakao, Shinji
在一些骨髓衰竭（BMF）患者中可以检测到糖基磷脂酰肌醇锚定蛋白缺陷（GPI-AP-）T细胞，但这些细胞与BMF病理生理学之间的联系仍有待阐明。为了阐明GPI-AP- T细胞在BMF中的意义，使用高分辨率流式细胞术（FCM）检查了来自562名患者的外周血中CD 48-CD 59-CD 3+细胞的存在，并且GPI-AP- T细胞在其表型和对抑制分子（包括疱疹病毒进入介体（HVEM）和骨髓抑制细胞因子TGF-β）的敏感性方面进行了表征。多谱系FCM分析检测到72例（12.8%）患者的CD 48-CD 59-CD 3 + T细胞以及GPI-AP-髓样细胞。出乎意料的是，12例患者（10例再生障碍性贫血和2例骨髓增生异常综合征-难治性贫血，2.1%），表现出与其他具有GPI-AP-髓样细胞的BMF患者相似的临床特征，例如对免疫抑制治疗的良好反应，仅在T细胞中显示0.01-0.3%的GPI-AP-细胞。CD 48-CD 59- T细胞主要由效应记忆（EM）和末端效应细胞组成，而来自接受抗CD 52抗体的非BMF患者的CD 48-CD 59- T细胞仅显示EM和中枢记忆表型。TGF-β和HVEM能够通过其GPI-AP CD 160连接抑制T细胞增殖，其在体外抑制GPI-AP+ T细胞的增殖比来自相同患者的GPI-AP- T细胞的增殖更有效。因此，GPI-AP- T细胞以及GPI-AP-骨髓细胞的存在可能反映了BMF的免疫病理生理学，其中通过GPI-AP型受体发生了精氨酸介导的造血干细胞抑制。
Glycosylphosphatidylinositol-anchored protein-deficient (GPI-AP-) T cells can be detected in some patients with bone marrow failure (BMF), but the link between these cells and BMF pathophysiology remains to be elucidated. To clarify the significance of GPI-AP- T cells in BMF, peripheral blood from 562 patients was examined for the presence of CD48-CD59-CD3+ cells using high-resolution flow cytometry (FCM), and the GPI-AP- T cells were characterized with regard to their phenotype and sensitivity to inhibitory molecules, including herpesvirus entry mediator (HVEM) and a myelosuppressive cytokine, TGF-beta. A multi-lineage FCM analysis detected CD48-CD59-CD3+ T cells in 72 (12.8%) of the patients, together with GPI-AP- myeloid cells. Unexpectedly, 12 patients (10 with aplastic anemia and 2 with myelodysplastic syndrome-refractory anemia, 2.1%), who showed clinical features similar to those of other BMF patients with GPI-AP- myeloid cells, such as a good response to immunosuppressive therapy, displayed 0.01-0.3% GPI-AP- cells exclusively in T cells. The CD48-CD59- T cells consisted of predominantly effector memory (EM) and terminal effector cells, while CD48-CD59- T cells from non-BMF patients who had received anti-CD52 antibody only showed EM and central memory phenotypes. TGF-beta and HVEM capable of inhibiting T-cell proliferation via its GPI-AP CD160 ligation suppressed the in vitro proliferation of GPI-AP+ T cells more potently than that of GPI-AP- T cells from the same patients. The presence of GPI-AP- T cells, as well as GPI-AP- myeloid cells, may therefore reflect the immunopathophysiology of BMF in which cytokine-mediated suppression of hematopoietic stem cells via GPI-AP-type receptors takes place.