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

Fas (CD95/Apo-1) exists both in membrane-bound and in biologically active s oluble (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 sFa s by AML blasts may then function as a protective mechanism by competing wi th membrane-bound Fas for binding sites on the common Fas ligand (FasL). sF as 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 derive d from acute leukemia patients with therapy-induced leukopenia and (ii) all ostimulated activation of T cells derived from normal donors. However, loca l in vivo levels of sFas will also be influenced by variations in systemic levels. High serum levels of sFas were detected ill acute leukemia patients during chemotherapy-induced cytopenia, but these levels decreased during c omplicating bacterial infections. In contrast, serum levels of sFasL were n ormal in leukopenic patients. The present results support the hypothesis th at local release of sFas can function as a protective mechanism against AM L-reactive T cells, but the effects of this local release are, in addition, modulated by variations: in systemic levels of sFas (but not sFasL).