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Laboratoire de Biologie et Pathologie des Déficits Immunitaires and Laboratoire d'Immunologie Cellulaire de l'Ecole Pratique des Hautes Etudes, Faculté de Médecine et Hôpital Pitié-Salpêtrière, Paris, France
Key Words. Human • Dendritic cells • Differentiation • Apoptosis • Hematopoiesis
Dr. Bruno Canque, Laboratoire d'Immunologie, CERVI, Hôpital de la Pitié-Salpêtrière, 83 Blvd. de l'Hôpital, 75651 Paris CEDEX 13, France.
We analyzed the effect of tumor necrosis factor (TNF)-
on the differentiation and viability of dendritic cells (DC) generated from cord blood CD34+ progenitors cultured for five days with GM-CSF, Flt-3 ligand (FL), and stem cell factor (SCF), and then with GM-CSF only [TNF(–) cultures]. Adding TNF- from the start [TNF(+) cultures] potentiated progenitor cell proliferation and promoted early differentiation of CD1a+ DC precursors without affecting differentiation of CD14+ cells, which comprise bipotent precursors of DC and macrophages, nor of CD15+ granulocytic cells. Use of TNF- was associated with increased cell mortality, which peaked on culture day 10 and mainly involved CD1a+ DC. Selective apoptosis of CD1a+ DC precursors was confirmed by showing that survival of day-7-sorted CD1a+CD14– cells from TNF(+) cultures was lower than that of CD1a–CD14+ cells. That similar findings were noted for sorted CD1a+CD14– cells of TNF(–) cultures, further cultured with GM-CSF without or with TNF-, indicates that apoptosis of CD1a+ DC precursors was not induced by TNF-. Apoptosis of CD1a+ DC precursors occurred after the cells had lost the capacity to incorporate bromodeoxyuridin. Finally, using higher GM-CSF concentrations or adding interleukin 3 (IL-3) improved viability of CD1a+ cells. Other cytokines, such as IL-4 and transforming growth factor (TGF)-ß1, were ineffective in this respect, though they promoted differentiation of CD1a+ DC. These results indicate that TNF- promotes the differentiation of CD1a+ DC precursors, which display a high susceptibility to apoptosis that can be prevented by high concentrations of GM-CSF or use of IL-3, without affecting the differentiation of the CD14+ DC precursors.
This article has been cited by other articles:
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  A. M. Woltman, C. Massacrier, J. W. de Fijter, C. Caux, and C. van Kooten Corticosteroids Prevent Generation of CD34+-Derived Dermal Dendritic Cells But Do Not Inhibit Langerhans Cell Development J. Immunol., June 15, 2002; 168(12): 6181 - 6188. [Abstract] [Full Text] [PDF]
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 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]
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M. Rosenzwajg, L. Tailleux, and J. C. Gluckman CD13/N-aminopeptidase is involved in the development of dendritic cells and macrophages from cord blood CD34+ cells Blood, January 15, 2000; 95(2): 453 - 460. [Abstract] [Full Text] [PDF]
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B. Canque, Y. Bakri, S. Camus, M. Yagello, A. Benjouad, and J. C. Gluckman The Susceptibility to X4 and R5 Human Immunodeficiency Virus-1 Strains of Dendritic Cells Derived In Vitro From CD34+ Hematopoietic Progenitor Cells Is Primarily Determined by Their Maturation Stage Blood, June 1, 1999; 93(11): 3866 - 3875. [Abstract] [Full Text] [PDF]
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