The unique profile of cord blood natural killer cells balances incomplete maturation and effective killing function upon activation

被引:125
|
作者
Luevano, Martha [1 ,2 ]
Daryouzeh, Mehri [1 ,2 ]
Alnabhan, Rehab [1 ,2 ]
Querol, Sergio [1 ,2 ,3 ]
Khakoo, Salim [4 ]
Madrigal, Alejandro [1 ,2 ]
Saudemont, Aurore [1 ,2 ]
机构
[1] UCL, London NW3 2QG, England
[2] Anthony Nolan Res Inst, London NW3 2QG, England
[3] Programa Concordia Banc Sang & Teixits, Barcelona, Spain
[4] Univ London Imperial Coll Sci Technol & Med, Dept Med, London SW7 2AZ, England
关键词
Natural killer cells; Cord blood; Immunotherapy; Hematopoietic stem cell transplantation; VERSUS-HOST-DISEASE; COMPLEX CLASS-I; NK-CELLS; LYMPHOCYTE SUBSETS; SELF-TOLERANCE; NOD/SCID MICE; BONE-MARROW; T-CELLS; TRANSPLANTATION; CD56(BRIGHT);
D O I
10.1016/j.humimm.2011.12.015
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cord blood (CB) is increasingly used as a source of stem cells for hematopoietic stem cell transplantation, and natural killer (NM) cells may be the effectors of the antileukemic response observed after CB transplantation. Here, we analyzed the phenotype and functions of CB NM cell subsets. We determined that the percentage of NK cells was higher in CB compared with peripheral blood (PB). Furthermore, there was a higher percentage of the CD56(bright) subset in CB. CB NK cells reached a late stage of differentiation, but exhibited higher expression of NKG2A and expressed fewer killer-cell immunoglobulin-like receptors, suggesting an incomplete maturation. CB NM cells highly expressed CXCR4, but did not express L-selectin, highlighting unique homing properties of CB NM cells. CB NM cells proliferated in response to interleukin-2 and degranulated in response to stimulation with tumor cells, but failed to lyse K562 cells in Cr-51-release assay. CB NM cells exhibited a lower interferon-gamma production in comparison with PB NM cells. Culture with IL-2 increased CB NM cell functions. Our study sheds light on CB NM cell properties and highlights the potential of CB as a source of NM cells for immunotherapy. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:248 / 257
页数:10
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