IL-12 indirectly enhances proliferation of 5-FU-treated human hematopoietic peripheral blood CD34+ cells.
Interleukin-12 (IL-12) or natural killer cell stimulatory factor (NKSF), has multiple effects on T lymphocytes and natural killer cells. In this study, the effect of IL-12 on human hematopoiesis was studied by analyzing the growth of CD34+ peripheral blood stem cells (PBSC), in steady state. In the presence of Epo, IL-12 alone or in combination with IL-3 or SCF had no effect on the formation of colonies from CD34+ cells. In culture with Epo, G-CSF, and IL-3, the effect of Flt3-ligand (FL) on CD34+ PBSC was investigated in the presence or absence of IL-12. No additional effect of IL-12 was observed when combined with FL. We evaluated 5-FU-treated human CD34+ PBSC proliferation in cultures with Epo, G-CSF, and IL-3, in the presence or absence of IL-12. No cytokine combination enhanced colony formation from 5-FU-treated CD34+ cells. However, in cultures of 5-FU-treated human CD34+ cells, the most efficient combination was IL-3 + Epo + G-CSF + Accessory cells (CD34-). Furthermore, IL-12 enhanced this colony formation significantly. To investigate whether immature CD34+ cells were responsible for FL or SCF, 5-FU-treated human CD34+ cells were cultured with or without IL-12. Whereas no synergistic effect was observed in combination with IL-12, SCF alone significantly enhanced colony formation. However, the colony number was found to be smaller than with the potent combination of accessory cells in the presence of IL-12. These results indicate that accessory cells, lost in CD34+ cell purification, could be partly responsible for an IL-12 effect on immature human PBSC proliferation.
Grafte
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Research Department of Hematopoietic and Tumor Differenciation (DIFEMA), University School of Medicine and Pharmacy, Saint-Etienne du Rouvray, France.
Lévêque
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Paysant
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Vasse
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Soria
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Vannier
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JP
D000328:Adult; D018952:Antigens, CD34 / Q000097:blood*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D008565:Membrane Proteins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology
D018952:Antigens, CD34; D000964:Antimetabolites, Antineoplastic; D008565:Membrane Proteins; D011994:Recombinant Proteins; D019089:Stem Cell Factor; C084881:flt3 ligand protein; D018664:Interleukin-12; D005472:Fluorouracil