Human T, B, natural killer, and dendritic cells arise from a common bone marrow progenitor cell subset

Galy, Anne; Travis, Marilyn; Cen, Dazhi; Chen, Benjamin

doi:10.1016/1074-7613(95)90175-2

Cited by 634 publications

(470 citation statements)

References 39 publications

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“…These intermediates are not merely a result of culture artifact since similar cells were found in fresh UCB, a site of developing hematopoiesis. This study agrees with our earlier work [30] and work published by others suggesting that heterogeneous CD34 + populations can be divided into a number of lymphoid precursors based on the expression of CD45RA, CD161, CD117 (c-kit) and CD127 (the IL7 receptor) [32][33][34]. Testing these markers with the expression of NK cell receptors was especially informative to further characterize the CD34 − /CD56 − /CD7 + population.…”

Section: Discussionsupporting

confidence: 92%

Mouse fetal and embryonic liver cells differentiate human umbilical cord blood progenitors into CD56-negative natural killer cell precursors in the absence of interleukin-15

McCullar

Oostendorp

Panoskaltsis‐Mortari

et al. 2008

Experimental Hematology

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Objective-Human NK cell maturation involves the orderly acquisition of NK cell receptors. Our aim was to understand how stromal interactions and cytokines are important in this developmental process.Methods-Human UCB CD34 + /Lin − /CD38 − cells were cultured on two murine stromal cell lines (AFT024 and EL08-1D2) in a switch culture to study NK cell development.Results-When human progenitors were cultured on AFT024 with IL-3 and Flt3-L in the absence of IL-15, NK cell differentiation occurred, albeit at low frequency. These conditions favored the accumulation of CD56 − NK cell precursors (CD34 + CD7 − , CD34 + CD7 + and CD34 − CD7 + cells), which are populations rare in adult blood but abundant in fresh UCB. In secondary culture, addition of IL-3 or IL-3+Flt3L to IL-15 increased the absolute number of CD56 + NK cells from precursors and the acquisition of CD94 and KIR. To further explore the microenvironment in early NK cell maturation, a cell line derived from murine embryonic liver (EL08-1D2) was studied. NK cell development and KIR acquisition was superior with EL08-1D2 which supported the differentiation of NK cell precursors, NK cell commitment, and proliferation.Conclusion-Although the earliest events in NK cell maturation do not require exogenous human IL-15, it is required at a later stage of NK cell commitment. At a minimum, murine stroma, IL-3, and Flt3-L are required to recapitulate early NK cell development and differentiation into distinct NK cell precursors. EL08-1D2 induces KIR acquisition suggesting that extrinsic signals in NK cell development are conserved between mouse and man.

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Section: Discussionsupporting

confidence: 92%

Mouse fetal and embryonic liver cells differentiate human umbilical cord blood progenitors into CD56-negative natural killer cell precursors in the absence of interleukin-15

McCullar

Oostendorp

Panoskaltsis‐Mortari

et al. 2008

Experimental Hematology

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“…Here, we show that human TdT ϩ CD34 ϩ CD10 Ϫ CD19 Ϫ cells represent a stable population in chimeric bone marrow. Marked up-regulation of four genes required for B lymphocyte formation occurred at the presumptive next stage of differentiation and this CD34 ϩ CD10 ϩ CD19 Ϫ fraction is thought to include the human counterparts of common lymphoid progenitors (28). That is, cells with these characteristics may have the potential for differentiation in T, B, NK, and dendritic lineages, but reduced ability to generate myeloid progenitors.…”

Section: Discussionmentioning

confidence: 99%

“…1, A and B). CD34 ϩ CD10 ϩ CD19 Ϫ cells that are potential common lymphoid progenitors (28) represented another easily resolved category (Fig. 1, A and B), and RT-PCR analysis of sorted marrow cells (Fig.…”

Section: Engraftment and Normal Differentiation Of Human Cells In Nodmentioning

confidence: 99%

Relatively Normal Human Lymphopoiesis but Rapid Turnover of Newly Formed B Cells in Transplanted Nonobese Diabetic/SCID Mice

Rossi

Medina

Garrett

et al. 2001

The Journal of Immunology

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Human B lineage lymphocyte precursors in chimeric nonobese diabetic/SCID mice transplanted with umbilical cord blood cells were directly compared with those present in normal bone marrow. All precursor subsets were represented and in nearly normal proportions. Cell cycle activity and population dynamics were investigated by staining for the Ki-67 nuclear Ag as well as by incorporation experiments using 5-bromo-2′-deoxyuridine. Again, this revealed that human B lymphopoiesis in chimeras parallels that in normal marrow with respect to replication and progression through the lineage. Moreover, sequencing of Ig gene rearrangement products showed that a diverse repertoire of VH genes was utilized by the newly formed lymphocytes but there was no evidence for somatic hypermutation. The newly formed B cells frequently acquired the CD5 Ag and had a short life span in the periphery. Thus, all molecular requirements for normal B lymphocyte formation are present in nonobese diabetic/SCID mice, but additional factors are needed for recruitment of B cells into a fully mature, long-lived pool. The model can now be exploited to learn about species restricted and conserved environmental cues for human B lymphocyte production.

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“…Alternatively, PBMC cultured with GM-CSF and IL-4 can transiently differentiate into DC-like cells (13,14). DC can also arise from the most immature T cell precursors or bone marrow progenitors, which can also generate NK and B cells but not cells of the myeloid lineage (17)(18)(19). Interestingly, GM-CSF does not appear to be necessary for DC generation from lymphoid-committed precursors (19, 19a).…”

mentioning

confidence: 99%

“…The lineage derivation of DC remains controversial, but there is growing evidence that DC can be subdivided into myeloid-derived (8)(9)(10)(11)(12)(13)(14)(15)(16)(17) and lymphoid-derived populations (17)(18)(19). The myeloid relationship of DC is based mainly upon in vitro experimentation.…”

mentioning

confidence: 99%

Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified.

Maraskovsky¹,

Brasel²,

Teepe³

et al. 1996

The Journal of Experimental Medicine

1,024

773

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SummaryDendritic cells (DC) are the most efficient APC for T cells. The clinical use of DC as vectors for anti-tumor and infectious disease immunotherapy has been limited by their trace levels and accessibility in normal tissue and terminal state of differentiation. In the present study, daily injection of human Flt3 ligand (Flt3L) into mice results in a dramatic numerical increase in cells co-expressing the characteristic DC markers--class II MHC, CD11c, DEC205, and CD86. In contrast, in mice treated with either GM-CSF, GM-CSF plus IL-4, c-kit ligand (c-kltL), or G-CSF, class II ÷ CDllc ÷ cells were not significantly increased. Five distinct DC subpopulations were identified in the spleen of Flt3L-treated mice using CDSot and CD11b expression. These cells exhibited veiled and dendritic processes and were as efficient as rare, mature DC isolated from the spleens of untreated mice at presenting allo-Ag or soluble Ag to T cells, or in priming an Ag-specific T cell response in vivo. Dramatic numerical increases in DC were detected in the bone marrow, gastro-intestinal lymphoid tissue (GALT), liver, lymph nodes, lung, peripheral blood, peritoneal cavity, spleen, and thymus. These results suggest that Flt3L could be used to expand the numbers of functionally mature DC in vivo for use in clinical immunotherapy.

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Human T, B, natural killer, and dendritic cells arise from a common bone marrow progenitor cell subset

Cited by 634 publications

References 39 publications

Mouse fetal and embryonic liver cells differentiate human umbilical cord blood progenitors into CD56-negative natural killer cell precursors in the absence of interleukin-15

Mouse fetal and embryonic liver cells differentiate human umbilical cord blood progenitors into CD56-negative natural killer cell precursors in the absence of interleukin-15

Relatively Normal Human Lymphopoiesis but Rapid Turnover of Newly Formed B Cells in Transplanted Nonobese Diabetic/SCID Mice

Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified.

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