Functional expression of Fas antigen (CD95) on hematopoietic progenitor cells

We investigated the expression of an apoptosis-associated antigen (Fas) (CD95) on hematopoietic progenitor cells in the presence or absence of interferon-γ (IFN-γ) and/or tumor necrosis factor-α (TNF-α). CD34⁺ cells freshly isolated from bone marrow did not express Fas. However, IFN-γ and/or TNF-α induced the expression of both the mRNA of Fas and Fas itself in a dose-dependent fashion on the surface of CD34⁺ cells after 48 hours of serum-free culture. IFN-γ and TNF-α had a synergistic effect on the induction of Fas, when both cytokines were added to the culture. The TNF-α- induced Fas expression is mediated by p55 TNF-α receptor. CD34⁺ cells cultured in medium alone or with stem cell factor (SCF) showed some slight expression of Fas. When anti-Fas antibody (IgM) was added to CD34⁺ cells after the induction of Fas expression, CD34⁺ cells underwent apoptosis, as shown by a decrease in the number of viable cells, morphologic changes, the induction of DNA fragmentation, and a decrease in the number of colony- forming cells (CFC) including colony-forming unit granulocytes/macrophages (CFU-GM) and burst-forming unit erythroids (BFU-E). These observations indicate that IFN-γ and/or TNF-α, well known as negative hematopoietic regulators, induce functional Fas on hematopoietic progenitor cells. The suppression of hematopoiesis by negative hematopoietic regulators may be mediated in part by Fas induction.