SUPPRESSION OF ALLOANTIGEN-INDUCED T-CELL PROLIFERATION BY CD14(-COLONY-STIMULATING FACTOR-MOBILIZED PERIPHERAL-BLOOD MONONUCLEAR-CELLS() CELLS DERIVED FROM GRANULOCYTE)
M. Mielcarek et al., SUPPRESSION OF ALLOANTIGEN-INDUCED T-CELL PROLIFERATION BY CD14(-COLONY-STIMULATING FACTOR-MOBILIZED PERIPHERAL-BLOOD MONONUCLEAR-CELLS() CELLS DERIVED FROM GRANULOCYTE), Blood, 89(5), 1997, pp. 1629-1634
The proliferative responsiveness of granulocyte colony-stimulating fac
tor (G-CSF)-mobilized blood was studied in uni-directional mixed leuko
cyte cultures. Unfractionated mononuclear cells from mobilized blood o
btained by leukapheresis at day 4 after initiation of G-CSF (G-PBMC) w
ere hyporesponsive (31.5%+/-9.2% response, P=.003) compared to mononuc
lear cells obtained from the peripheral blood before administration of
G-CSF (preG-PBMC). There was great variability among donors when puri
fied 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 cell
s derived from leukapheresis products (G-CD14 cells) suppressed alloan
tigen-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 w
as largely contact-independent. PreG- and G-CD14 cells had equivalent
potency in suppressing proliferative responses. Given that G-CSF-mobil
ized blood cell grafts contain 50-fold more CD14 cells and only 10-fol
d more T cells than marrow, we propose that suppression of donor T cel
ls by the large proportion of monocytes present in leukapheresis produ
cts could contribute to the unexpectedly low incidence and severity of
graft-versus-host disease after peripheral blood stem cell transplant
ation. (C) 1997 by The American Society of Hematology.