FAS ANTIGEN EXPRESSION ON CD34(-CELLS IS INDUCED BY INTERFERON-GAMMA AND TUMOR-NECROSIS-FACTOR-ALPHA AND POTENTIATES CYTOKINE-MEDIATED HEMATOPOIETIC SUPPRESSION IN-VITRO() HUMAN MARROW)
J. Maciejewski et al., FAS ANTIGEN EXPRESSION ON CD34(-CELLS IS INDUCED BY INTERFERON-GAMMA AND TUMOR-NECROSIS-FACTOR-ALPHA AND POTENTIATES CYTOKINE-MEDIATED HEMATOPOIETIC SUPPRESSION IN-VITRO() HUMAN MARROW), Blood, 85(11), 1995, pp. 3183-3190
Activation of Fas antigen, a cell surface receptor molecule, by its li
gand results in transduction of a signal for cell death. The fas syste
m has been implicated in target cell recognition, clonal development o
f immune effector cells, and termination of the cellular immune respon
se. Fas antigen expression on lymphocytes is regulated by interferon g
amma (IFN gamma) and tumor necrosis factor alpha (TNF alpha), cytokine
s that also have inhibitory effects on hematopoiesis, We investigated
Fas antigen expression on human marrow cells and the effects of Fas ac
tivation on hematopoiesis in vitro, Freshly isolated immature hematopo
ietic cells, as defined by the CD34 marker, did not express Fas antige
n at levels detectable by fluorescent staining, CD34(+) cells, which i
nclude progenitors and stem cells, showed low levels of Fas expression
in culture, even in the presence of growth factors, Stimulation by TN
F alpha and IFN gamma markedly increased Fas antigen expression on CD3
4(+) cells, Anti-Fas antibody, which mimics the action of the putative
ligand, enhanced IFN gamma- and TNF alpha-mediated suppression of col
ony formation by bone marrow (BM) in a dose-dependent manner. This eff
ect did not require the presence of accessory cells, Colony formation
from mature (CD34(+) CD38(+)) and immature (CD34(+) CD38(-)) progenito
r cells and long-term culture initiating cells were susceptible to the
inhibitory action of anti-fas antibody in the presence of IFN gamma a
nd TNF alpha. Apoptosis assays performed on total BM cells and CD34(+)
cells showed that anti-fas antibody induced programmed cell death of
CD34(+) BM cells. Fas antigen may be expressed as part of the differen
tiation program of hematopoietic cells. Fas antigen and its ligand may
play a role in the pathophysiology of marrow failure states and in th
e elimination of abnormal hematopoietic cells in the course of an immu
ne response. (C) 1995 by The American Society of Hematology.