scholarly journals Interleukin-3 cooperates with tumor necrosis factor alpha for the development of human dendritic/Langerhans cells from cord blood CD34+ hematopoietic progenitor cells

Blood ◽  
1996 ◽  
Vol 87 (6) ◽  
pp. 2376-2385 ◽  
Author(s):  
C Caux ◽  
B Vanbervliet ◽  
C Massacrier ◽  
I Durand ◽  
J Banchereau
Keyword(s):  
Tumor Necrosis Factor ◽  
Cord Blood ◽  
Progenitor Cells ◽  
Langerhans Cells ◽  
Tumor Necrosis ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Gm Csf ◽  
Cord Blood Cd34 ◽  
Necrosis Factor

We have previously shown that tumor necrosis factor (TNF)alpha strongly potentiates the granulocyte-macrophage colony-stimulating factor (GM- CSF)/interleukin (IL)-3-dependent proliferation of CD34+ hematopoietic progenitor cells (HPC) through the recruitment of early progenitors with high proliferative potential. Furthermore, the combination of GM- CSF and TNFalpha allows the generation of large numbers of dendritic/Langerhans cells (D-Lc). Herein, we analyzed whether IL-3, when combined to TNFalpha would, as does GM-CSF, allow the generation of CD1a+ D-Lc. Accordingly, cultures of cord blood CD34+ HPC with IL-3 + TNFalpha yielded 20% to 60% CD14+ cells and 11% to 17% CD1a+ cells, while IL-3 alone did not generate significant numbers of CD1a+ cells. Although the percentage of CD1a+ cells detected in IL3 + TNFalpha was lower than that observed in GM-CSF + TNFalpha (42% to 78%), the strong growth induced by IL-3 + TNFalpha generated as many CD1a+ cells as did GM-CSF + TNFalpha. The CD14+ and CD1a+ cells generated with IL-3 + TNFalpha are similar to CD14+ and CD1a+ cells generated in GM-CSF alone and GM-CSF + TNFalpha, respectively. CD1a+ cells differed from CD14+ cells by (1) dendritic morphology, (2) higher expression of CD1a, CD1c, CD4, CD40, adhesion molecules (CD11c, CD54, CD58), major histocompatibility complex (MHC) class II molecules and CD28 ligands (CD80 and CD86), (3) lack of Fc receptor FcgammaRI (CD64) and complement receptor CR1 (CD35) expression, and (4) stronger induction of allogeneic T-cell proliferation. Thus, in combination with TNFalpha, IL-3 is as potent as GM-CSF for the generation of CD1a+ D-Lc from cord blood CD34+ HPC. The dendritic cell inducing ability of IL-3 may explain why mice with inactivated GM-CSF gene display dendritic cells.

Neutralization of Tumor Necrosis Factor Activity Shortly After the Onset of Dendritic Cell Hematopoiesis Reveals a Novel Mechanism for the Selective Expansion of the CD14-Dependent Dendritic Cell Pathway

Blood ◽  
1998 ◽  
Vol 92 (3) ◽  
pp. 745-755 ◽  
Author(s):  
Frances Santiago-Schwarz ◽  
Marguerite McCarthy ◽  
John Tucci ◽  
Steven E. Carsons
Keyword(s):  
Dendritic Cell ◽  
Tumor Necrosis Factor ◽  
Progenitor Cells ◽  
Tumor Necrosis ◽  
Interleukin 4 ◽  
Differentiation Potential ◽  
Dc System ◽  
Gm Csf ◽  
American Society ◽  
Necrosis Factor

The CD14-dependent and -independent dendritic cell (DC) pathways are instituted simultaneously when CD34+ progenitor cells are treated with granulocyte-macrophage colony-stimulating factor (GM-CSF)/tumor necrosis factor (TNF) ± stem cell factor (SCF) (GTS). If TNF activity is neutralized within 48 hours of cytokine exposure, DC development is halted and myelogranulocytic hematopoiesis takes place. In this study, we show that disruption of TNF activity at a later time point produced a distinct alteration within the DC system. Instead of downregulating DC development, treatment of GTS cultures with antibodies to TNF (anti-TNF) on day 3 provoked the selective expansion of the CD14-dependent (monocyte) DC pathway from progenitor cell populations lacking CD14 and CD1a. After an initial decrease in proliferation, anti-TNF produced a rebound in cell growth that yielded intermediate myeloid progenitors exhibiting CD14-dependent DC differentiation potential and CD14+CD1a+ DC precursors. Cultures enriched in CD14-dependent DCs were more potent stimulators of a mixed leukocyte reaction, compared with control GTS cultures containing both types of DCs. The intermediate progenitors expanded in the presence of anti-TNF were CD115+CD33+DR+, long-lived, and displayed clonogenic potential in methylcellulose. When exposed to the appropriate cytokine combinations, these cells yielded granulocytes, monocytes, and CD14-dependent DCs. Antigen-presenting function was acquired only when DC maturation was induced from these myelodendritic progenitors with GM-CSF + interleukin-4 or GTS. These studies show a novel mechanism by which TNF regulates the DC system, as well as providing a strategy for the amplification of the CD14-dependent DC pathway from immature progenitors. Although TNF is required to ensure the institution of DC hematopoiesis from CD34+ progenitor cells, its activity on a later progenitor appears to limit the development of CD14-dependent DCs. © 1998 by The American Society of Hematology.

Retroviral-Mediated Gene Transduction of c-kit Into Single Hematopoietic Progenitor Cells From Cord Blood Enhances Erythroid Colony Formation and Decreases Sensitivity to Inhibition by Tumor Necrosis Factor- and Transforming Growth Factor-β1

Blood ◽  
1999 ◽  
Vol 94 (7) ◽  
pp. 2319-2332 ◽  
Author(s):  
Li Lu ◽  
Michael C. Heinrich ◽  
Li-Sheng Wang ◽  
Mu-Shui Dai ◽  
Amy J. Zigler ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Progenitor Cells ◽  
Colony Formation ◽  
Tumor Necrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Gm Csf ◽  
Cd34 Cells ◽  
Necrosis Factor

The c-kit receptor and its ligand, steel factor (SLF), are critical for optimal hematopoiesis. We evaluated effects of transducing cord blood (CB) progenitor cells with a retrovirus encoding humanc-kit cDNA. CD34+ cells were sorted as a population or as 1 cell/well for cells expressing high levels of CD34+++ and different levels of c-kit (++, +, Lo/−), transduced and then cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), IL-6, erythropoietin (Epo) +/− SLF in the absence of serum. At a single-cell level, transduction with c-kit, but not with control (neo only), virus significantly increased colony formation, especially by erythroid and multipotential progenitors. The enhancing effect of c-kit transduction was inversely correlated with expression of c-kit protein before transduction. The greatest enhancing effects were noted in CD34+++kitLo/− cells transduced with c-kit. The stimulating effect was apparent even in the absence of exogenously added SLF, but in the presence of GM-CSF, IL-3, IL-6, and Epo. Enzyme-linked immunosorbent assay (ELISA) of SLF protein, reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of SLF mRNA expression in CD34+ cells, and use of neutralizing antibodies to SLF and/or c-kit suggested the presence of endogenous, although probably very low level, expression of SLF by these progenitor cells. Transduction of c-kit significantly decreased sensitivity of progenitor cells to the inhibitory effects of transforming growth factor-β1 and tumor necrosis factor-.c-kit–transduced cells had increased expression ofc-kit protein and decreased spontaneous or cytokine-induced apoptosis. Our results suggest that transduced c-kit into selected progenitor cells can enhance proliferation and decrease apoptosis and that endogenous SLF may mediate this effect.

scholarly journals Tumor necrosis factor-alpha strongly potentiates interleukin-3 and granulocyte-macrophage colony-stimulating factor-induced proliferation of human CD34+ hematopoietic progenitor cells

Blood ◽  
1990 ◽  
Vol 75 (12) ◽  
pp. 2292-2298 ◽  
Author(s):  
C Caux ◽  
S Saeland ◽  
C Favre ◽  
V Duvert ◽  
P Mannoni ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Tumor Necrosis ◽  
Marrow Cell ◽  
Hematopoietic Progenitor Cells ◽  
Tnf Alpha ◽  
Hematopoietic Progenitor ◽  
Short Term ◽  
Liquid Cultures ◽  
Interleukin 3 ◽  
Gm Csf

Previous studies have shown that tumor necrosis factors (TNFs) inhibit the proliferative effects of crude or purified colony-stimulating factors (CSFs) on low density human bone marrow cell fractions. In the present study we investigated the effects of TNF alpha on the growth of highly purified CD34+ human hematopoietic progenitor cells (HPC) in response to recombinant CSFs. In short-term liquid cultures (5 to 8 days), TNF alpha strongly potentiates interleukin-3 (IL-3) and granulocyte-macrophage-CSF (GM-CSF)-induced growth of CD34+ HPC, while it has no proliferative effect per se. Within 8 days, the number of viable cells obtained in TNF alpha-supplemented cultures is threefold higher than in cultures carried out with IL-3 or GM-CSF alone. Secondary liquid cultures showed that the potentiating effect of TNF alpha on IL-3-induced proliferation of CD34+ HPC does not result from an IL-3-dependent generation of TNF alpha responsive cells. Limiting dilution analysis indicates that TNF alpha increases both the frequency of IL-3 responding cells and the average size of the IL-3-dependent clones. The potentiating effect of TNF alpha on IL-3- and GM-CSF- dependent growth of CD34+ HPC is also observed in day 7 colony assays. Under these short-term culture conditions, TNF alpha does not appear to accelerate cell maturation as a precursor morphology is retained. Finally, TNF alpha inhibits the relatively weak growth-promoting effect of granulocyte-CSF (G-CSF), which acts on a more committed subpopulation of CD34+ HPC different from that recruited by IL-3 and GM- CSF. TNF beta displays the same modulatory effects as TNF alpha. Thus, TNFs appear to enhance the early stages of myelopoiesis.

Sign in / Sign up

Export Citation Format

Share Document