Stem cell factor and the regulation of dendritic cell production from CD34+ progenitors in bone marrow and cord blood.
Dendritic cells (DC) are essential for the presentation of antigen in primary immune responses and they develop from CD34+ cells in the bone marrow. Although both granulocyte macrophage colony stimulating factor (GM-CSF) and tumour necrosis factor (TNF) are known to stimulate the development of mature DC from their progenitor (CFU-DL), the function of stem cell factor (SCF) in this pathway remains to be determined. The interactions of SCF with GM-CSF, TNF, interleukin-3 (IL-3) and macrophage colony stimulating factor (M-CSF) in promoting CFU-DL development have now been studied in serum-free cultures of unfractionated as well as progenitor enriched cells from either bone marrow or cord blood. Although SCF alone is without effect on colony formation, it enhances both the numbers and size of DC colonies generated in vitro by GM-CSF and TNF. It acts directly on progenitors and in the presence of GM-CSF can also induce suboptimal DC growth even in the absence of TNF. SCF appears to recruit very early progenitors of a high proliferative potential with the capacity to differentiate into erythroid and myeloid as well as dendritic cell progeny. In combination with other cytokines it may therefore be useful for the ex vivo generation of large numbers of DC for clinical purposes.
Saraya
K
K
Northwick Park Hospital, Harrow, Middlesex, UK.
Reid
C D
CD
D018952:Antigens, CD34 / Q000097:blood; D001854:Bone Marrow Cells; D003713:Dendritic Cells / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood / Q000166:cytology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018952:Antigens, CD34; D007377:Interleukin-3; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor