Soluble Fas/Apo-1 (CD95) levels during T cell activation in the presence of acute myelogenous leukemia accessory cells; contributions from local release and variations in systemic levels |
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Authors: | Øystein Bruserud Elling Ulvestad |
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Institution: | (1) Section of Hematology, Department of Medicine, Haukeland University Hospital, N-5021 Bergen, Norway Tel.: +47-55-29-80-60 Fax: +47-55-97-29-50, NO;(2) Division for Immunology, Department of Microbiology, Haukeland University Hospital, Bergen, Norway, NO;(3) University of Bergen, Bergen, Norway, NO |
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Abstract: | Fas (CD95/Apo-1) exists both in membrane-bound and in biologically active soluble (s) forms. Ligation of membrane-expressed
Fas can induce apoptosis, and Fas-mediated signaling seems to be involved in T-cell-induced apoptosis of human acute myelogenous
leukemia (AML) blasts. The local release of sFas by AML blasts may then function as a protective mechanism by competing with
membrane-bound Fas for binding sites on the common Fas ligand (FasL). sFas was released by AML blasts during in vitro culture,
and this release was modulated by several cytokines that can be secreted by activated T cells. Increased levels of sFas could
be detected during in vitro activation of T cells in the presence of native AML accessory cells, and this was observed both
for (i) mitogenic activation of CD4+ and CD8+ T cell clones derived from acute leukemia patients with therapy-induced leukopenia and (ii) allostimulated activation of
T cells derived from normal donors. However, local in vivo levels of sFas will also be influenced by variations in systemic
levels. High serum levels of sFas were detected in acute leukemia patients during chemotherapy-induced cytopenia, but these
levels decreased during complicating bacterial infections. In contrast, serum levels of sFasL were normal in leukopenic patients.
The present results support the hypothesis that local release of sFas can function as a protective mechanism against AML-reactive
T cells, but the effects of this local release are, in addition, modulated by variations in systemic levels of sFas (but not
sFasL).
Received: 9 March 2000 / Accepted: 25 May 2000 |
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Keywords: | Acute myelogenous leukemia T lymphocyte Fas/Apo-1 (CD95) Fas ligand |
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