Dekojová Tereza, Houdová Lucie, Fatka Jiří, Pitule Pavel, Ostašov Pavel, Caputo Valentina S, Gmucová Hana, Lysák Daniel, Jindra Pavel, Holubová Monika
Department of Haematology and Oncology, University Hospital Pilsen, 304 60 Pilsen, Czech Republic.
Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University, 301 66 Pilsen, Czech Republic.
J Clin Med. 2020 Oct 29;9(11):3502. doi: 10.3390/jcm9113502.
Killer-immunoglobulin-like receptors (KIRs) are critical natural killer (NK) cell regulators. The expression of KIRs is a dynamic process influenced by many factors. Their ligands-HLA(Human Leukocyte Antigen) class I molecules-are expressed on all nucleated cells that keep NK cells under control. In hematopoietic stem cell transplantation (HSCT), NK cells play an essential role in relapse protection. In the presented pilot study, we characterized the dynamic expression of inhibitory KIRS (iKIRs), which protect cells against untoward lysis, in donors and patients during the first three months after HSCT using flow cytometry. The expression of all iKIRs was highly variable and sometimes correlated with patients' clinical presentation and therapy regiment. Cyclophosphamide (Cy) in the graft-versus-host disease (GvHD) prevention protocol downregulated KIR2DL1 to just 25% of the original donor value, and the FEAM (Fludarabine + Etoposid + Ara-C + Melphalan) conditioning protocol reduced KIR2DL3. In lymphoid neoplasms, there was a slightly increased KIR2DL3 expression compared to myeloid malignancies. Additionally, we showed that the ex vivo activation of NK cells did not alter the level of iKIRs. Our study shows the influence of pre- and post-transplantation protocols on iKIR expression on the surface of NK cells and the importance of monitoring their cell surface.
杀伤免疫球蛋白样受体(KIRs)是关键的自然杀伤(NK)细胞调节因子。KIRs的表达是一个受多种因素影响的动态过程。它们的配体——人类白细胞抗原(HLA)I类分子——在所有有核细胞上表达,从而控制NK细胞。在造血干细胞移植(HSCT)中,NK细胞在预防复发方面起着至关重要的作用。在本初步研究中,我们使用流式细胞术对HSCT后前三个月供体和患者中抑制性KIRs(iKIRs)的动态表达进行了表征,iKIRs可保护细胞免受不当裂解。所有iKIRs的表达高度可变,有时与患者的临床表现和治疗方案相关。移植物抗宿主病(GvHD)预防方案中的环磷酰胺(Cy)将KIR2DL1下调至仅为原始供体值的25%,而氟达拉滨+依托泊苷+阿糖胞苷+美法仑(FEAM)预处理方案降低了KIR2DL3的表达。在淋巴瘤中,与髓系恶性肿瘤相比,KIR2DL3的表达略有增加。此外,我们表明NK细胞的体外激活并未改变iKIRs的水平。我们的研究显示了移植前后方案对NK细胞表面iKIR表达的影响以及监测其细胞表面的重要性。
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