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异基因造血干细胞移植后自然杀伤细胞上抑制性杀伤免疫球蛋白样受体的动态变化:一项初步研究。

Dynamic Changes of Inhibitory Killer-Immunoglobulin-Like Receptors on NK Cells after Allogeneic Hematopoietic Stem Cell Transplantation: An Initial Study.

作者信息

Dekojová Tereza, Houdová Lucie, Fatka Jiří, Pitule Pavel, Ostašov Pavel, Caputo Valentina S, Gmucová Hana, Lysák Daniel, Jindra Pavel, Holubová Monika

机构信息

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.

出版信息

J Clin Med. 2020 Oct 29;9(11):3502. doi: 10.3390/jcm9113502.


DOI:10.3390/jcm9113502
PMID:33138211
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7692795/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804d/7692795/c576616ff86d/jcm-09-03502-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804d/7692795/a19084201d6f/jcm-09-03502-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804d/7692795/7645c79dbc0a/jcm-09-03502-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804d/7692795/6d756cd00d22/jcm-09-03502-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804d/7692795/c8f02d59a760/jcm-09-03502-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804d/7692795/106e44079986/jcm-09-03502-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804d/7692795/c576616ff86d/jcm-09-03502-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804d/7692795/a19084201d6f/jcm-09-03502-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804d/7692795/7645c79dbc0a/jcm-09-03502-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804d/7692795/6d756cd00d22/jcm-09-03502-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804d/7692795/c8f02d59a760/jcm-09-03502-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804d/7692795/106e44079986/jcm-09-03502-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804d/7692795/c576616ff86d/jcm-09-03502-g006.jpg

相似文献

[1]
Dynamic Changes of Inhibitory Killer-Immunoglobulin-Like Receptors on NK Cells after Allogeneic Hematopoietic Stem Cell Transplantation: An Initial Study.

J Clin Med. 2020-10-29

[2]
Donor and host coexpressing KIR ligands promote NK education after allogeneic hematopoietic stem cell transplantation.

Blood Adv. 2019-12-23

[3]
The Education of NK Cells Determines Their Responsiveness to Autologous HIV-Infected CD4 T Cells.

J Virol. 2019-11-13

[4]
[Immunoediting of natural killer cells by human nasopharyngeal carcinoma cell line: altered expression of KIRs and NKG2D receptors leads to reduction of natural killer cell-mediated cytolysis].

Nan Fang Yi Ke Da Xue Xue Bao. 2007-3

[5]
Donor-recipient killer immunoglobulin like receptor (KIR) genotype matching has a protective effect on chronic graft versus host disease and relapse incidence following HLA-identical sibling hematopoietic stem cell transplantation.

Ann Hematol. 2018-6

[6]
[Clinical relevance of KIRs in hematopoietic stem cell transplantation].

Med Pregl. 2010

[7]
Recipient expression of ligands for donor inhibitory KIRs enhances NK-cell function to control leukemic relapse after haploidentical transplantation.

Eur J Immunol. 2015-8

[8]
Haploidentical Natural Killer Cells Infused before Allogeneic Stem Cell Transplantation for Myeloid Malignancies: A Phase I Trial.

Biol Blood Marrow Transplant. 2016-7

[9]
Reconstitution of natural killer cell receptor repertoires after unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation: analyses of CD94:NKG2A and killer immunoglobulin-like receptor expression and their associations with clinical outcome.

Biol Blood Marrow Transplant. 2007-6

[10]
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Arch Immunol Ther Exp (Warsz). 2016-12

引用本文的文献

[1]
NK- and T-cell repertoire is established early after allogeneic HSCT and is imprinted by CMV reactivation.

Blood Adv. 2024-11-12

[2]
NK cell defects: implication in acute myeloid leukemia.

Front Immunol. 2023

本文引用的文献

[1]
Estimation of German KIR Allele Group Haplotype Frequencies.

Front Immunol. 2020

[2]
Study of KIR gene expression at the mRNA level in specific donor-derived NK cells after allogeneic HSCT.

Immunogenetics. 2020-1-3

[3]
Regulation of KIR3DL3 Expression via Mirna.

Genes (Basel). 2019-8-9

[4]
Improving the Clinical Application of Natural Killer Cells by Modulating Signals Signal from Target Cells.

Int J Mol Sci. 2019-7-15

[5]
Killer Ig-Like Receptors (KIRs): Their Role in NK Cell Modulation and Developments Leading to Their Clinical Exploitation.

Front Immunol. 2019-5-28

[6]
Downregulation of MHC Class I Expression by Influenza A and B Viruses.

Front Immunol. 2019-5-29

[7]
Allele-Level Genotyping of More Than a Million Samples: Workflow, Algorithm, and Observations.

Front Immunol. 2018-12-4

[8]
Mass Cytometry for the Assessment of Immune Reconstitution After Hematopoietic Stem Cell Transplantation.

Front Immunol. 2018-7-26

[9]
A phase 1 study of lirilumab (antibody against killer immunoglobulin-like receptor antibody KIR2D; IPH2102) in patients with solid tumors and hematologic malignancies.

Oncotarget. 2018-4-3

[10]
Next generation natural killer cells for cancer immunotherapy: the promise of genetic engineering.

Curr Opin Immunol. 2018-3-30

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