Analysis of natural killer (NK) cell activity and adhesion molecules on NK cells from umbilical cord blood

Tanaka, Hidehisa; Kai, Shunro; Yamaguchi, Masao; Misawa, Mahito; Fujimori, Yoshihiro; Yamamoto, Masuji; Hara, Hiroshi

doi:10.1034/j.1600-0609.2003.00081.x

Cited by 66 publications

(70 citation statements)

References 42 publications

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“…In this study, NK cells were purified by negative immunomagnetic selection to prevent any NK cell activation before experiments were undertaken, and a purity Ͼ97% was obtained. In agreement with previous reports (20,22,23,28), the spontaneous cytotoxic activity of CB mononuclear cells against NK-sensitive targets is lower than that of adult mononuclear cells. Our data show that the cytolytic activity of purified CB NK cells is also lower, suggesting that the difference in cytotoxic activity against NK-sensitive targets between CB and adult blood may be attributed to intrinsic differences in NK cells themselves.…”

Section: Cd56supporting

confidence: 81%

“…One recent study reported that the expression of adhesion molecules is reduced on CD56 dim CB NK cells (20). However, this study did not investigate the full range of phenotypic and functional markers of NK cell maturation.…”

mentioning

confidence: 69%

“…The differences between CB and adult blood observed in these reports may not be related to specific properties of CB NK cells but rather to modulation by other cells, such as IL-12-and IL-15-producing monocytes (22,29). Two studies using purified NK cells reported only spontaneous cytotoxicity of CD3 Ϫ cells, CD16 ϩ CD56 ϩ cells, and CD56 dim and CD56 bright subpopulations obtained by positive selection or complement-based negative selection (20,30). To our knowledge, our study is the first to investigate proliferation, IFN-␥ production, and cytotoxicity of CB CD3 Ϫ…”

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confidence: 99%

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Characterization of Cord Blood Natural Killer Cells: Implications for Transplantation and Neonatal Infections

et al. 2005

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The role of natural killer (NK) cells in hematopoietic stem cell transplantation and in the control of neonatal infections is not yet clear. Donor-versus-recipient NK cell alloreactivity was found to improve outcome in some settings of hematopoietic stem cell transplantation. We hypothesized that the role of NK cells in cord blood (CB) transplantation and neonatal infections may depend on CB NK cell maturation stage. We therefore analyzed the expression of NK cell differentiation/phenotypic markers in human CB, as well as functional properties of purified CB NK cells. CD8 and CD57 expression was lower in CB than in adult NK cells. However, the expression of other differentiation markers was similar, as was cell surface density of CD56, the percentage of late NK cell precursors, interferon-␥ production, and the proliferative response of purified NK cells to IL-2. Spontaneous cytotoxic activity of purified CB NK cells against NK-sensitive targets was low but reached adult levels after treatment with IL-15. Expression of perforin and granzyme B was higher in CB NK cells (90 versus 58% and 86 versus 69%, respectively Natural killer (NK) cells are innate immune lymphocytes defined by their cell surface expression of the CD56 antigen without expression of the CD3 antigen. They display a broad anti-infectious and antitumor cytolytic activity. They can also secrete various cytokines, such as interferon (IFN)-␥ and other cytokines that regulate the immune response and hematopoiesis (1). Although NK cells play an important role early in the infectious cycle, at a time when specific immunity has not yet fully developed, their role in the defense of the neonate against infection has not been studied (2). It was demonstrated recently that NK cells play an important role in the outcome of clinical HLA-haploidentical hematopoietic stem cell transplantation (1,3). A positive effect of NK cell alloreactivity has also been reported in a series of unrelated hematopoietic stem cell transplantations (4). We, as several other groups, use cord blood (CB) as a source of stem cells in partially HLA-mismatched transplantation with outcomes similar to those observed in HLA-identical bone marrow transplantation (5-9). CB contains a higher percentage of NK cells than adult blood-, bone marrow-, or cytokine-mobilized peripheral blood stem cell grafts (10). It thus is tempting to speculate that neonatal/CB NK cells may play a role in CB transplantation as well as in the control of neonatal infections.Several markers of NK cell immaturity have been described. Among these is the level of cell-surface expression of CD56.

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Section: Cd56supporting

confidence: 81%

mentioning

confidence: 69%

mentioning

confidence: 99%

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Characterization of Cord Blood Natural Killer Cells: Implications for Transplantation and Neonatal Infections

et al. 2005

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“…Our findings confirm results from previous studies showing that the CD56 bright CD16 +/2 and CD56 dim CD16 + subsets are present in the same proportions in both CB and PB [33,34]. Nevertheless, these studies also reported that CB NK cells have a natural reduced killing ability as compared with PB NK cells.…”

Section: Discussionsupporting

confidence: 82%

Defining Early Human NK Cell Developmental Stages in Primary and Secondary Lymphoid Tissues

Eissens

Spanholz

Meer

et al. 2012

Transplantation Journal

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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 +/2 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.

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“…Immature NK cell precursors (eg in peripheral blood after allogeneic bone marrow transplantation and in umbilical cord blood) are predominantly CD56 pos /CD16 neg , during NK cell differentiation CD16 expression increases with impact on NK cell functionality. [29][30][31][32][33][34] In all tests, no considerable expression of CD107a was detected on CD56 dim /CD16 pos cells, indicating that these cells do not degranulate in response to NK-sensitive leukemia targets and do not exhibit direct cytotoxicity. Since CD16 surface expression is crucial for antibody-dependent cellular cytotoxicity, it is reasonable that the CD56 dim /CD16 pos cells are the major effector cells mediating this type of cytotoxic response.…”

Section: Discussionmentioning

confidence: 99%

CD56dimCD16neg cells are responsible for natural cytotoxicity against tumor targets

et al. 2005

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The activation of natural killer (NK) cells leads to degranulation and secretion of cytotoxic granula. During this process, the lytic granule membrane protein CD107a becomes detectable at the cell surface. Based on this phenomenon, we have analyzed by a novel flow cytometry-based assay, the number and phenotype of NK cells responding to tumor targets. Using human leukemia and lymphoma cell lines, we observed a close correlation between CD107a surface expression and target cell lysis, indicating that NK cell cytotoxicity can be assessed by this method. The number of degranulating NK cells was closely related to the ratio of effector and target cells and showed a maximum at a ratio of 1:1. Moreover, we were able to show that the population of CD56 dim /CD16 neg NK cells is primarily responsible for the cytotoxic activity against tumor targets whereas neither CD56 dim /CD16 pos nor CD56 bright NK cells degranulated in response to the cell lines. Our results indicate that the CD107a assay represents a promising new method for the quantification and characterization of cells exhibiting natural cytotoxicity.

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Analysis of natural killer (NK) cell activity and adhesion molecules on NK cells from umbilical cord blood

Cited by 66 publications

References 42 publications

Characterization of Cord Blood Natural Killer Cells: Implications for Transplantation and Neonatal Infections

Characterization of Cord Blood Natural Killer Cells: Implications for Transplantation and Neonatal Infections

Defining Early Human NK Cell Developmental Stages in Primary and Secondary Lymphoid Tissues

CD56dimCD16neg cells are responsible for natural cytotoxicity against tumor targets

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