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Suppression of alloantigen-induced T-cell proliferation by CD14+ cells
derived from granulocyte colony-stimulating factor-mobilized peripheral
blood mononuclear cells
M Mielcarek, PJ Martin and B Torok-Storb
Clinical Research Division, Fred Hutchinson Cancer Research Center,
Seattle, WA 98104, USA.
The proliferative responsiveness of granulocyte colony-stimulating factor
(G-CSF)-mobilized blood was studied in uni-directional mixed leukocyte
cultures. Unfractionated mononuclear cells from mobilized blood obtained by
leukapheresis at day 4 after initiation of G-CSF (G- PBMC) were
hyporesponsive (31.5% +/- 9.2% response, P = .003) compared to mononuclear
cells obtained from the peripheral blood before administration of G-CSF
(preG-PBMC). There was great variability among donors when purified preG-
and G-CD4 cells were compared. In eight of 10 donors, G-CD4 cells were
equally responsive or moderately hyporesponsive; in two of 10 donors, G-CD4
cells were more strikingly hyporesponsive. CD14 cells derived from
leukapheresis products (G-CD14 cells) suppressed alloantigen-induced
proliferation by 48.6% +/- 7.5% when added to preG-PBMC or preG-CD4 cells
at responder-CD14 ratios of 2:1 (P < .001). Suppression was evident
(14.4% +/- 5.0%) even at responder-CD14 ratios of 8:1 and was largely
contact-independent. PreG- and G-CD14 cells had equivalent potency in
suppressing proliferative responses. Given that G-CSF-mobilized blood cell
grafts contain 50-fold more CD14 cells and only 10-fold more T cells than
marrow, we propose that suppression of donor T cells by the large
proportion of monocytes present in leukapheresis products could contribute
to the unexpectedly low incidence and severity of graft-versus-host disease
after peripheral blood stem cell transplantation.
Volume 89,
Issue 5,
pp. 1629-1634,
03/01/1997
Copyright © 1997 by The American Society of Hematology
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