CLL-cells induce IDOhi CD14+HLA-DRlo myeloid-derived suppressor cells that inhibit T-cell responses and promote TRegs
CLL-cells induce IDOhi CD14+HLA-DRlo myeloid-derived suppressor cells that inhibit T-cell responses and promote TRegs
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DOI：
10.1182/blood-2013-12-546416
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发表时间：
2014-07-31
期刊：
影响因子：
20.3
通讯作者：
Mougiakakos, Dimitrios
中科院分区：
文献类型：
--
作者：
Jitschin, Regina;Braun, Martina;Mougiakakos, Dimitrios
髓源性抑制细胞（MDSCs）是一种异质细胞群，具有一定的特征，包括异常的髓源性表型和抑制T细胞的能力。MDSCs主要在恶性疾病中被研究，研究结果表明其参与肿瘤相关的免疫抑制。慢性淋巴细胞白血病（CLL）是成人发病率最高的白血病。免疫缺陷早在疾病早期就已经出现，并影响临床病程。我们评估了未经治疗的CLL患者中缺乏HLA-DR表达的循环CD14（+）细胞（HLA-DRlo）的存在、频率、与其他免疫参数的关联以及功能特性。这些单核细胞代表了最明确的人类MDSC亚群之一。CD14(+) HLA-DRlo细胞的频率在CLL患者中显著增加。此外，MDSCs抑制体外T细胞活化并诱导抑制性调节性T细胞（TRegs）。mdsc介导的T细胞调节可能归因于它们增加的吲哚胺2,3-双加氧酶（IDO）活性。CLL细胞诱导来自健康供体单核细胞的IDOhi MDSCs，表明CLL细胞、MDSCs和treg之间存在双向串扰。总的来说，我们发现在CLL中MDSC群体扩大。导致这种积累的确切机制仍有待阐明，测试CLL MDSCs的拮抗抑制功能是否可以代表增强免疫反应的一种手段将是一项有趣的研究。
Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population that shares certain characteristics including an aberrant myeloid phenotype and the ability to suppress T cells. MDSCs have been predominantly studied in malignant diseases and findings suggest involvement in tumor-associated immune suppression. Chronic lymphocytic leukemia (CLL) is the leukemia with the highest incidence among adults. Immune defects occur already at early disease stages and impact the clinical course. We assessed presence, frequency, association to other immune parameters, and functional properties of circulating CD14(+) cells lacking HLA-DR expression (HLA-DRlo) in patients with untreated CLL. These monocytic cells represent one of the best-defined human MDSC subsets. Frequency of CD14(+) HLA-DRlo cells was significantly increased in CLL patients. Furthermore, MDSCs suppressed in vitro T-cell activation and induced suppressive regulatory T cells (TRegs). The MDSC-mediated modulation of T cells could be attributed to their increased indoleamine 2,3-dioxygenase (IDO) activity. CLL cells induced IDOhi MDSCs from healthy donor monocytes suggesting bidirectional crosstalk between CLL-cells, MDSCs, and TRegs. Overall, we identified a MDSC population that expands in CLL. The exact mechanisms responsible for such accumulation remain to be elucidated and it will be of interest to test whether antagonizing suppressive functions of CLL MDSCs could represent a mean for enhancing immune responses.