Combined and sequential effects of human IL-3 and GM-CSF on the
proliferation of CD34+ hematopoietic cells from cord blood
S Saeland, C Caux, C Favre, V Duvert, MJ Pebusque, P Mannoni and JE deVries
UNICET, Laboratory for Immunological Research, Dardilly, France.
The proliferative effects of recombinant human interleukin-3 (IL-3) and
granulocyte-macrophage colony-stimulating factor (GM-CSF) were investigated
in semi-solid and liquid cultures of purified CD34+ hematopoietic cells
obtained from umbilical cord blood. No important differences in overall
cloning efficiencies in response to IL-3 or GM- CSF were observed in
semi-solid medium in the presence of erythropoietin (Ep). However, GM-CSF
was less effective for the development of erythroid bursts (BFU-E), and
only IL-3 was observed to induce significant numbers of mixed-erythroid
colonies (E-MIX). Both IL- 3 and GM-CSF also induced proliferation of CD34+
in liquid cultures. Proliferative responses to IL-3 were found to be more
rapid and stronger than to GM-CSF, although the number of initial
responsive cells as judged by autoradiography were comparable. Enhanced
proliferation of CD34+ cells both in semi-solid and liquid cultures was
obtained in the presence of combinations of IL-3 and GM-CSF. The responses
observed were less than additive, with the exception of the development of
eosinophil colonies and clusters, where IL-3 and GM-CSF were found to act
synergistically. In secondary cultures, proliferative responses to GM-CSF
were strongly enhanced by preculture of CD34+ cells in IL-3 for four to 11
days, and to a lesser extent by preculture in GM- CSF. Finally, responses
to IL-3 were not affected by preculture of CD34+ cells in the presence of
GM-CSF. Our results indicate that there is a wide overlap of cells capable
of proliferating either in response to IL-3 or to GM-CSF within the cord
blood CD34+ compartment. However, differences in primary proliferation
kinetics and increased responsiveness to GM-CSF following preculture
suggest the importance of a sequential action of IL-3 and GM-CSF in the
expansion of CD34+ cells.
Volume 73,
Issue 5,
pp. 1195-1201,
04/01/1989
Copyright © 1989 by The American Society of Hematology