The Fas Death Factor
10 Mar 1995-Science (American Association for the Advancement of Science)-Vol. 267, Iss: 5203, pp 1449-1456
TL;DR: 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.
Abstract: 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.
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TL;DR: This work was supported in part by Grants-in-Aid from the Ministry of Education, Science, and Culture of Japan and by a Research Grant from the Princess Takamatsu Cancer Research Fund, and performed in part through Special Coordination Funds of the Science and Technology Agency of the Japanese Government.
5,054 citations
Cites background from "The Fas Death Factor"
...Thus, although per-for CTL-mediated cytotoxicity (Nagata and Golstein, 1995)....
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...The extracellular region of the TNF receptor al., 1993; Nagata and Golstein, 1995), which includes family members carries 2–6 repeats of a cysteine-rich TNF, lymphotoxin, CD30 ligand, 4-1BB ligand, CD40 subdomain that has about 25% similarity among various ligand, CD27 ligand, and TRAIL…...
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TL;DR: It is reported here that, except for cells of the macrophage lineage, normal human tissues do not express B7-H1 and the findings have implications for the design of T cell–based cancer immunotherapy.
Abstract: B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in the regulation of cellular and humoral immune responses through the PD-1 receptor on activated T and B cells. We report here that, except for cells of the macrophage lineage, normal human tissues do not express B7-H1. In contrast, B7-H1 is abundant in human carcinomas of lung, ovary and colon and in melanomas. The pro-inflammatory cytokine interferon-gamma upregulates B7-H1 on the surface of tumor cell lines. Cancer cell-associated B7-H1 increases apoptosis of antigen-specific human T-cell clones in vitro, and the apoptotic effect of B7-H1 is mediated largely by one or more receptors other than PD-1. In addition, expression of B7-H1 on mouse P815 tumor increases apoptosis of activated tumor-reactive T cells and promotes the growth of highly immunogenic B7-1(+) tumors in vivo. These findings have implications for the design of T cell-based cancer immunotherapy.
4,290 citations
Cites background from "The Fas Death Factor"
...In addition, 624mel cells do not express the proteins FasL or TRAIL, which are known to participate in the induction of T-cell apoptosi...
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TL;DR: The authors regret the inability to cite all of the primary literature contributing to this review due to length considerations, but wish to thank F. Chan, T. Migone, and J. Wang for insightful comments on the manuscript.
3,756 citations
Cites background from "The Fas Death Factor"
...Fas-mediated cytotoxicity is the major calcium-independent killing mechanism ofundergo heavy chain class switching to produce differ- CD81 cytotoxic T cells (Nagata and Golstein, 1995)....
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TL;DR: A caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD) have now been identified in the cytoplasmic fraction of mouse lymphoma cells and seems to function as a chaperone for CAD during its synthesis, remaining complexed with CAD to inhibit its DNase activity.
Abstract: The homeostasis of animals is regulated not only by the growth and differentiation of cells, but also by cell death through a process known as apoptosis. Apoptosis is mediated by members of the caspase family of proteases, and eventually causes the degradation of chromosomal DNA. A caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD) have now been identified in the cytoplasmic fraction of mouse lymphoma cells. CAD is a protein of 343 amino acids which carries a nuclear-localization signal; ICAD exists in a long and a short form. Recombinant ICAD specifically inhibits CAD-induced degradation of nuclear DNA and its DNase activity. When CAD is expressed with ICAD in COS cells or in a cell-free system, CAD is produced as a complex with ICAD: treatment with caspase 3 releases the DNase activity which causes DNA fragmentation in nuclei. ICAD therefore seems to function as a chaperone for CAD during its synthesis, remaining complexed with CAD to inhibit its DNase activity; caspases activated by apoptotic stimuli then cleave ICAD, allowing CAD to enter the nucleus and degrade chromosomal DNA.
3,248 citations
TL;DR: This work utilized nano-electrospray tandem mass spectrometry to identify CAP3 and CAP4, components of the CD95 (Fas/APO-1) death-inducing signaling complex, and found a novel 55 kDa protein, designated FLICE, which has homology to both FADD and the ICE/CED-3 family of cysteine proteases.
3,181 citations
Cites background from "The Fas Death Factor"
...Recent studies ongranzyme Bsuggest thatblood leukocytes, which was consistent with the imporcytotoxic lymphocytes may utilize this secreted serinetant role of CD95-signaling in lymphocyte homeostasis protease to activate directly members of the ICE/CED-3(Nagata and Golstein, 1995)....
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References
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TL;DR: The Ipr mice develop lymphadenopathy and suffer from a systemic lupus erythematosus-like autoimmune disease, indicating an important role for Fas antigen in the negative selection of autoreactive T cells in the thymus.
Abstract: Fas antigen is a cell-surface protein that mediates apoptosis. It is expressed in various tissues including the thymus and has structural homology with a number of cell-surface receptors, including tumour necrosis factor receptor and nerve growth factor receptor. Mice carrying the lymphoproliferation (lpr) mutation have defects in the Fas antigen gene. The lpr mice develop lymphadenopathy and suffer from a systemic lupus erythematosus-like autoimmune disease, indicating an important role for Fas antigen in the negative selection of autoreactive T cells in the thymus.
2,988 citations
TL;DR: Complementary DNAs encoding the cell surface antigen Fas were isolated from a cDNA library of human T cell lymphoma KT-3 cells and revealed that the molecule coding for the Fas antigen determinant is a 319 amino acid polypeptide with a single transmembrane domain.
2,918 citations
TL;DR: For some mammalian cells, programmed death seems to occur by default unless suppressed by signals from other cells, so dependence on specific survival signals provides a simple way to eliminate misplaced cells, for regulating cell numbers and, perhaps, for selecting the fittest cells.
Abstract: Programmed cell death occurs in most animal tissues at some stage of their development, but the molecular mechanism by which it is executed is unknown. For some mammalian cells, programmed death seems to occur by default unless suppressed by signals from other cells. Such dependence on specific survival signals provides a simple way to eliminate misplaced cells, for regulating cell numbers and, perhaps, for selecting the fittest cells. But how general is this dependence on survival signals?
2,667 citations
TL;DR: Northern hybridization revealed that Fas ligand is expressed in activated splenocytes and thymocytes, consistent with its involvement in T cell-mediated cytotoxicity and in several nonlymphoid tissues, such as testis.
2,600 citations
TL;DR: The CD8+ effector cells raised in the CD4 subset- deficient host were able of clear vital tissues from productive infection and to restrict asymptomatic, persistent infection to acinar glandular epithelial cells in salivary gland tissue.
Abstract: We have established a murine model system for exploring the ability of a CD4 subset-deficient host to cope with cytomegalovirus infection, and reported three findings. First, an antiviral response of the CD8 subset of T lymphocytes could be not only initiated but also maintained for a long period of time despite a continued absence of the CD4 subset, whereas the production of antiviral antibody proved strictly dependent upon help provided by the CD4 subset. Second, no function in the defense against infection could be ascribed as yet to CD4-CD8- T lymphocytes, which were seen to accumulate to a new subset as a result of depletion of the CD4 subset. This newly arising subset did not substitute for CD4+ T lymphocytes in providing help to B lymphocytes, and was also not effective in controlling the spread of virus in host tissues. As long as a function of these cells in the generation and maintenance of a CD8 subset-mediated response is not disproved, caution is indicated with concern to an autonomy of the CD8 subset. Third, even though with delay, the CD8+ effector cells raised in the CD4 subset-deficient host were able of clear vital tissues from productive infection and to restrict asymptomatic, persistent infection to acinar glandular epithelial cells in salivary gland tissue.
2,175 citations