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Tumor necrosis factor-alpha strongly potentiates interleukin-3 and
granulocyte-macrophage colony-stimulating factor-induced proliferation of
human CD34+ hematopoietic progenitor cells
C Caux, S Saeland, C Favre, V Duvert, P Mannoni and J Banchereau
Laboratory for Immunological Research, Schering-Plough (UNICET) Dardilly,
France.
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.
Volume 75,
Issue 12,
pp. 2292-2298,
06/15/1990
Copyright © 1990 by The American Society of Hematology
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