Defining early human NK cell developmental stages in primary and secondary lymphoid tissues

A better understanding of human NK cell development in vivo is crucial to exploit NK cells for immunotherapy. Here, we identified seven distinctive NK cell developmental stages in bone marrow of single donors using 10-color flow cytometry and found that NK cell development is accompanied by early ex...

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Bibliographic Details
Published in:PloS one 2012-02, Vol.7 (2), p.e30930-e30930
Main Authors: Eissens, Diana N, Spanholtz, Jan, van der Meer, Arnold, van Cranenbroek, Bram, Dolstra, Harry, Kwekkeboom, Jaap, Preijers, Frank W M B, Joosten, Irma
Format: Article
Language:English
Subjects:
Analysis
Antigens, CD - biosynthesis
B cells
Blood
Bone marrow
Bone Marrow Cells
Bone marrow transplantation
Cancer
Cell Differentiation
Cell Movement
Compartments
Cord blood
Cytometry
Developmental stages
Fc receptors
Flow cytometry
Hematology
Heterogeneity
Humans
Immunoglobulins
Immunology
Immunophenotyping
Immunotherapy
Killer cells
Killer Cells, Natural - cytology
Laboratories
Lectins
Liver
Lymph
Lymph nodes
Lymphoid tissue
Lymphoid Tissue - cytology
Medicine
Natural killer cells
NKG2 antigen
Peripheral blood
Receptors
Receptors, Immunologic - biosynthesis
Rodents
Signaling Lymphocytic Activation Molecule Family
Spleen
T cell receptors
Tissues
Transplants & implants
Umbilical cord
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Summary:A better understanding of human NK cell development in vivo is crucial to exploit NK cells for immunotherapy. Here, we identified seven distinctive NK cell developmental stages in bone marrow of single donors using 10-color flow cytometry and found that NK cell development is accompanied by early expression of stimulatory co-receptor CD244 in vivo. Further analysis of cord blood (CB), peripheral blood (PB), inguinal lymph node (inLN), liver lymph node (liLN) and spleen (SPL) samples showed diverse distributions of the NK cell developmental stages. In addition, distinctive expression profiles of early development marker CD33 and C-type lectin receptor NKG2A between the tissues, suggest that differential NK cell differentiation may take place at different anatomical locations. Differential expression of NKG2A and stimulatory receptors (e.g. NCR, NKG2D) within the different subsets of committed NK cells demonstrated the heterogeneity of the CD56(bright)CD16⁺/⁻ and CD56(dim)CD16⁺ subsets within the different compartments and suggests that microenvironment may play a role in differential in situ development of the NK cell receptor repertoire of committed NK cells. Overall, differential in situ NK cell development and trafficking towards multiple tissues may give rise to a broad spectrum of mature NK cell subsets found within the human body.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0030930