Siemińska Izabela, Rutkowska-Zapała Magdalena, Bukowska-Strakova Karolina, Gruca Anna, Szaflarska Anna, Kobylarz Krzysztof, Siedlar Maciej, Baran Jarek
Department of Clinical Immunology, Institute of Paediatrics, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland.
Department of Anaesthesiology and Intensive Care, Institute of Paediatrics, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland.
Cent Eur J Immunol. 2018;43(4):413-420. doi: 10.5114/ceji.2018.81359. Epub 2018 Dec 31.
Transient hypogammaglobulinaemia of infancy (THI) is a primary immunodeficiency characterised by low levels of immunoglobulin G (often with concomitant decrease of IgA and sometimes also of IgM) with still unknown exact reason. A delayed normalisation of the immunoglobulin level in THI may be associated with a transiently elevated number of regulatory T cells (Treg). Although in cancer and chronic inflammation it was shown that the level of Treg cells can be increased by myeloid-derived suppressor cells (MDSCs), until now no studies have been performed in the context of the role of MDSCs in THI and their correlation with Treg cells. Consequently, we aimed to determine the occurrence of MDSCs in the peripheral blood of children with THI and correlate their level with the level of Treg cells.
Flow cytometry analyses of Mo-MDSCs and Gr-MDSCs, characterised as HLA-DRCD11bCD15CD14 and HLA-DRCD11bCD15CD14, respectively, and Treg (CD4CD25Foxp3) cells were performed.
The proportion of Mo-MDSCs and Gr-MDSCs was significantly higher in the group of THI patients with elevated level of Treg cells (from the 95% confidence interval level of healthy controls). The cells with Mo-MDSC and Gr-MDSC characteristics positively correlated with the level of Treg cells. Moreover, children with a higher proportion of circulating Treg cells, and thereby higher level of MDSCs, showed delayed normalisation of IgG level and recovery.
These findings show for the first time that MDSCs may be involved in the pathomechanism of THI, probably acting through the induction of Treg cells.
婴儿期短暂性低丙种球蛋白血症（THI）是一种原发性免疫缺陷病，其特征为免疫球蛋白G水平低下（常伴有IgA降低，有时IgM也降低），确切病因尚不清楚。THI中免疫球蛋白水平的延迟正常化可能与调节性T细胞（Treg）数量的短暂增加有关。尽管在癌症和慢性炎症中已表明髓源性抑制细胞（MDSC）可增加Treg细胞水平，但迄今为止，尚未有关于MDSC在THI中的作用及其与Treg细胞相关性的研究。因此，我们旨在确定THI患儿外周血中MDSC的存在情况，并将其水平与Treg细胞水平相关联。
对分别被表征为HLA-DR⁻CD11b⁺CD15⁺CD14⁻和HLA-DR⁻CD11b⁺CD15⁺CD14⁺的单核细胞源性MDSC（Mo-MDSC）和粒细胞源性MDSC（Gr-MDSC）以及Treg（CD4⁺CD25⁺Foxp3⁺）细胞进行流式细胞术分析。
Treg细胞水平升高的THI患者组中，Mo-MDSC和Gr-MDSC的比例显著高于健康对照组的95%置信区间水平。具有Mo-MDSC和Gr-MDSC特征的细胞与Treg细胞水平呈正相关。此外，循环Treg细胞比例较高，进而MDSC水平较高的儿童，其IgG水平正常化和恢复延迟。
这些发现首次表明MDSC可能参与THI的发病机制，可能通过诱导Treg细胞发挥作用。
