|
|
 Previous Article | Table of Contents | Next Article 
Differentiation of natural killer (NK) cells from human primitive marrow
progenitors in a stroma-based long-term culture system: identification of a
CD34+7+ NK progenitor
JS Miller, KA Alley and P McGlave
Division of Hematology, University of Minnesota Medical School, Minneapolis
55455.
We have recently described a marrow stroma-dependent long-term culture
system that supports differentiation of CD34+ human marrow primitive
progenitors into natural killer (NK) cells. We postulate that CD7
expression may be an early event in commitment of hematopoietic progenitors
to the NK lineage. Here we compare the characteristics of CD34+7- and
CD34+7+ marrow cells cultivated in the stroma-based NK culture system.
These CD34+ populations were further compared with a marrow derived, more
committed, CD34-7+ progenitor to emphasize the continuum of NK development
and to highlight differences between progenitors in our assays. No
progenitor proliferated when plated in media without stroma, underscoring
the importance of stroma in NK differentiation. Plating progenitor
populations in interleukin-2 containing media directly on preestablished,
allogeneic, irradiated marrow stroma for 5 weeks resulted in CD56+CD3- NK
cells; however, characteristics of the cultured populations differed. Fold
expansion and cloning efficiency of the CD34+7+ population, determined by a
functional limiting dilution assay was significantly higher than of the
CD34+7- or CD34+7+ populations. This suggests that the CD34+7+ population
is highly enriched for an NK progenitor and a possible intermediate in NK
lineage differentiation. Further dividing the CD34+7+ population by the
relative fluorescence of CD7 into CD34+7+dim and CD34+7+bright populations
showed that the CD34+7+bright population exhibited a significantly higher
cloning frequency than parallel experiments with CD34+7+dim cells (11.8%
+/- 2.4% v 2.4% +/- 0.7%, n = 6; P = .005). Plating of the more primitive
CD34+7- population in a transwell system (which separates progenitors from
stroma by a microporous membrane) prevents differentiation into NK cells.
In contrast, plating of CD34+7+ progenitors in transwells resulted in
generation of NK cells. These data suggest that primitive, but not more
mature NK progenitors may require direct contact with stroma for the
initial differentiation steps. Finally, differentiation of the NK
progenitors in this stroma-dependent model results in expression of CD2 not
present on any of the starting populations. This observation suggests that
marrow stroma can stimulate CD2 expression on NK progenitors in a
previously undescribed fashion that may be analogous to the thymic effect
on CD2 expression in immature T lymphocytes. These observations identify
early steps in the commitment of primitive marrow CD34+ hematopoietic
progenitors to a lymphoid lineage and underscore the importance of
coexpression of CD7 with CD34 as an early lymphoid commitment
characteristic and direct progenitor-stroma interactions in this process.
Volume 83,
Issue 9,
pp. 2594-2601,
05/01/1994
Copyright © 1994 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
B. Grzywacz, N. Kataria, M. Sikora, R. A. Oostendorp, E. A. Dzierzak, B. R. Blazar, J. S. Miller, and M. R. Verneris
Coordinated acquisition of inhibitory and activating receptors and functional properties by developing human natural killer cells
Blood,
December 1, 2006;
108(12):
3824 - 3833.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. W. Storms, P. D. Green, K. M. Safford, D. Niedzwiecki, C. R. Cogle, O. M. Colvin, N. J. Chao, H. E. Rice, and C. A. Smith
Distinct hematopoietic progenitor compartments are delineated by the expression of aldehyde dehydrogenase and CD34
Blood,
July 1, 2005;
106(1):
95 - 102.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. I. D. Rossi, T. Yokota, K. L. Medina, K. P. Garrett, P. C. Comp, A. H. Schipul Jr, and P. W. Kincade
B lymphopoiesis is active throughout human life, but there are developmental age-related changes
Blood,
January 15, 2003;
101(2):
576 - 584.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Sivori, M. Falco, E. Marcenaro, S. Parolini, R. Biassoni, C. Bottino, L. Moretta, and A. Moretta
Early expression of triggering receptors and regulatory role of 2B4 in human natural killer cell precursors undergoing in vitro differentiation
PNAS,
March 21, 2002;
(2002)
72065999.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Nakajima, R. Zhao, T. C. Lund, J. Ward, M. Dolan, B. Hirsch, and J. S. Miller
The BCR/ABL Transgene Causes Abnormal NK Cell Differentiation and Can Be Found in Circulating NK Cells of Advanced Phase Chronic Myelogenous Leukemia Patients
J. Immunol.,
January 15, 2002;
168(2):
643 - 650.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Miller and V. McCullar
Human natural killer cells with polyclonal lectin and immunoglobulinlike receptors develop from single hematopoietic stem cells with preferential expression of NKG2A and KIR2DL2/L3/S2
Blood,
August 1, 2001;
98(3):
705 - 713.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yu, M. Hagihara, K. Ando, B. Gansuvd, H. Matsuzawa, T. Tsuchiya, Y. Ueda, H. Inoue, T. Hotta, and S. Kato
Enhancement of Human Cord Blood CD34+ Cell-Derived NK Cell Cytotoxicity by Dendritic Cells
J. Immunol.,
February 1, 2001;
166(3):
1590 - 1600.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. A. Fehniger and M. A. Caligiuri
Interleukin 15: biology and relevance to human disease
Blood,
January 1, 2001;
97(1):
14 - 32.
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Canque, S. Camus, A. Dalloul, E. Kahn, M. Yagello, C. Dezutter-Dambuyant, D. Schmitt, C. Schmitt, and J. C. Gluckman
Characterization of dendritic cell differentiation pathways from cord blood CD34+CD7+CD45RA+ hematopoietic progenitor cells
Blood,
December 1, 2000;
96(12):
3748 - 3756.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. W. Storms, M. A. Goodell, A. Fisher, R. C. Mulligan, and C. Smith
Hoechst dye efflux reveals a novel CD7+CD34- lymphoid progenitor in human umbilical cord blood
Blood,
September 15, 2000;
96(6):
2125 - 2133.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Punzel, S.D. Wissink, J.S. Miller, K.A. Moore, I.R. Lemischka, and C.M. Verfaillie
The Myeloid-Lymphoid Initiating Cell (ML-IC) Assay Assesses the Fate of Multipotent Human Progenitors In Vitro
Blood,
June 1, 1999;
93(11):
3750 - 3756.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Miller, V. McCullar, M. Punzel, I. R. Lemischka, and K. A. Moore
Single Adult Human CD34+/Lin-/CD38- Progenitors Give Rise to Natural Killer Cells, B-Lineage Cells, Dendritic Cells, and Myeloid Cells
Blood,
January 1, 1999;
93(1):
96 - 106.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Takahashi, I. Miura, K. Saitoh, and A. B. Miura
Lineage Involvement of Stem Cells Bearing the Philadelphia Chromosome in Chronic Myeloid Leukemia in the Chronic Phase as Shown by a Combination of Fluorescence-Activated Cell Sorting and Fluorescence In Situ Hybridization
Blood,
December 15, 1998;
92(12):
4758 - 4763.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Saitoh, I. Miura, N. Takahashi, and A. B. Miura
Fluorescence In Situ Hybridization of Progenitor Cells Obtained by Fluorescence-Activated Cell Sorting for the Detection of Cells Affected by Chromosome Abnormality Trisomy 8 in Patients With Myelodysplastic Syndromes
Blood,
October 15, 1998;
92(8):
2886 - 2892.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Miller, V. McCullar, and C. M. Verfaillie
Ex Vivo Culture of CD34+/Lin-/DR- Cells in Stroma-Derived Soluble Factors, Interleukin-3, and Macrophage Inflammatory Protein-1alpha Maintains Not Only Myeloid But Also Lymphoid Progenitors in a Novel Switch Culture Assay
Blood,
June 15, 1998;
91(12):
4516 - 4522.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. M. Gaffney, J. Lund, and J. S. Miller
FLT-3 Ligand and Marrow Stroma-Derived Factors Promote CD3gamma , CD3delta , CD3zeta , and RAG-2 Gene Expression in Primary Human CD34+LIN-DR- Marrow Progenitors
Blood,
March 1, 1998;
91(5):
1662 - 1670.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. A. Fehniger, W. E. Carson, E. Mrozek, and M. A. Caligiuri
Stem Cell Factor Enhances Interleukin-2-Mediated Expansion of Murine Natural Killer Cells In Vivo
Blood,
November 1, 1997;
90(9):
3647 - 3653.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Miller, F. Prosper, and V. McCullar
Natural Killer (NK) Cells Are Functionally Abnormal and NK Cell Progenitors Are Diminished in Granulocyte Colony-Stimulating Factor-Mobilized Peripheral Blood Progenitor Cell Collections
Blood,
October 15, 1997;
90(8):
3098 - 3105.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Corrections for vol. 184, p. 1845
J. Exp. Med.,
March 17, 1997;
185(6):
1149 - 1150.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Sivori, M. Falco, E. Marcenaro, S. Parolini, R. Biassoni, C. Bottino, L. Moretta, and A. Moretta
Early expression of triggering receptors and regulatory role of 2B4 in human natural killer cell precursors undergoing in vitro differentiation
PNAS,
April 2, 2002;
99(7):
4526 - 4531.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
