Fas ligand (FasL), a cell surface molecule belonging to the tumor necrosis factor family, binds to its receptor Fas, thus inducing apoptosis of Fas-bearing cells. Various cells express Fas, whereas FasL is expressed predominantly in activated T cells. In the immune system, Fas and FasL are involved in down-regulation of immune reactions as well as in T cell-mediated cytotoxicity. Malfunction of the Fas system causes lymphoproliferative disorders and accelerates autoimmune diseases, whereas its exacerbation may cause tissue destruction.

https://science.sciencemag.org/content/sci/267/5203/1449.full.pdf

The Fas Death Factor

Identification and characterization of a new member of the TNF family that induces apoptosis

To evaluate the utility of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a cancer therapeutic, we created leucine zipper (LZ) forms of human (hu) and murine (mu) TRAIL to promote and stabilize the formation of trimers. Both were biologically active, inducing apoptosis of both human and murine target cells in vitro with similar specific activities. In contrast to the fulminant hepatotoxicity of LZ-huCD95L in vivo, administration of either LZ-huTRAIL or LZ-muTRAIL did not seem toxic to normal tissues of mice. Finally, repeated treatments with LZ-huTRAIL actively suppressed growth of the TRAIL-sensitive human mammary adenocarcinoma cell line MDA-231 in CB.17 (SCID) mice, and histologic examination of tumors from SCID mice treated with LZ-huTRAIL demonstrated clear areas of apoptotic necrosis within 9-12 hours of injection.

Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo

Apoptosis in the immune system is a fundamental process regulating lymphocyte maturation, receptor repertoire selection and homeostasis Thus, death by apoptosis is as essential for the function of lymphocytes as growth and differentiation This article focuses on death receptor-associated apoptosis and the role of CD95 (Apo-1/Fas)-mediated signalling in T-cell and B-cell development and during the course of an immune response Gaining an insight into these processes improves our understanding of the pathogenesis of diseases such as cancer, autoimmunity and AIDS, and opens new approaches to rational treatment strategies

CD95's deadly mission in the immune system

Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome

A significant proportion of previously activated human T cells undergo apoptosis when triggered through the CD3/T cell receptor complex, a process termed activation-induced cell death (AICD). Ligation of Fas on activated T cells by either Fas antibodies or recombinant human Fas-ligand (Fas-L) also results in cytolysis. We demonstrate that these two pathways of apoptosis are causally related. Stimulation of previously activated T cells resulted in the expression of Fas-L mRNA and lysis of Fas-positive target cells. Fas-L antagonists inhibited AICD of T cell clones and staphylococcus enterotoxin B (SEB)-specific T cell lines. The data indicate AICD in previously stimulated T cells is mediated by Fas/Fas-L interactions.

/pdf/fas-ligand-mediates-activation-induced-cell-death-in-human-t-iore646k8z.pdf

T Davis-Smith

Papers

Fas ligand mediates activation-induced cell death in human T lymphocytes.