Fas and Fas ligand: lpr and gld mutations

Nagata, Shinji; Suda, Takafumi

doi:10.1016/0167-5699(95)80069-7

Cited by 840 publications

(514 citation statements)

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“…25 Likewise, TRAIL expression in the human placenta has been associated with the maintenance of immune privilege. 26 Interestingly, however, while Fas (lpr) and FasL (gld) mutant mice show clear symptoms of uncontrolled immune cell activation, defects in cellular homeostasis, reduced apoptosis and development of autoimmune disease, 27 none of these signs is obvious in the TRAIL-deficient mouse, at least not at the first glance. 28,29 Yet, a more detailed analysis revealed that lack of TRAIL predisposes to increased susceptibility to the development of autoimmune diseases.…”

Section: Role Of Trail In Immune Regulation Immunopathologies and Aumentioning

confidence: 99%

TRAIL and immunity: more than a license to kill tumor cells

et al. 2004

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Section: Role Of Trail In Immune Regulation Immunopathologies and Aumentioning

confidence: 99%

TRAIL and immunity: more than a license to kill tumor cells

et al. 2004

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“…10 However, we did not detect alterations of Bcl-2 or Bax protein levels during induction of apoptosis in HSVtk-transduced murine B16F10 melanoma cells treated with GCV. In this study we have found that the apoptosis signal pathway of Fas (CD95/APO-1) receptor, Fas ligand (FasL) and associated regulators [11][12][13][14] can be induced and thus responsible for most of the cell killing by the HSVtk/GCV strategy in four different murine tumors including B16F10 melanoma, NG4TL4 sarcoma, H6 hepatoma and 1MEA 7R.1 hepatoma.…”

Section: Introductionmentioning

confidence: 96%

Involvement of Fas (CD95/APO-1) and Fas ligand in apoptosis induced by ganciclovir treatment of tumor cells transduced with herpes simplex virus thymidine kinase

Wei

Chao²,

Shih

et al. 1999

Gene Ther

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Transduction of cancer cells with herpes simplex virus thy-HSVtk-transduced tumor cells after the cell cycle arrest midine kinase gene (HSVtk) followed by prodrug gancicloand before apoptosis. Increased expression of FasL could vir (GCV) treatment has been shown to induce apoptosis. also be observed in vivo in HSVtk-transduced tumors In this study, four murine tumors including B16F10 melainduced to regress by GCV treatment. Enzyme measurenoma, NG4TL4 sarcoma, H6 hepatoma and 1MEA 7R.1 ments using specific substrate showed that the caspase-3 hepatoma were found to vary in sensitivity to this gene activation followed kinetically the FasL expression. More therapy strategy in vitro but, at effective doses of GCV, the than half of the HSVtk/GCV-induced cell death could be HSVtk-transduced cells of all four tumors showed similar abrogated by addition to the cell culture medium of a spekinetics of early rise in p53 protein levels, then cell cycle cific antisense oligonucleotide to block FasL synthesis, a S-/G2-phase arrest and finally signs of apoptosis. Immunorecombinant Fas/Fc chimeric protein to compete with Fas blot analyses revealed that Fas (CD95/APO-1), Fas ligand receptor for FasL binding, or cell-permeable specific tetra-(FasL) and two downstream mediators, RIP and caspase-3 peptide inhibitors of caspase-3 or caspase-8. (CPP32, YAMA, Apopain) were increased in GCV-treated

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“…2C). Despite the fact that FLIP S -overexpressing T cells were significantly protected against CD95L-induced cell death, lck FLIP S -transgenic mice did not develop a lymphadenopathy or age-dependent autoimmune disease typical for the lpr and gld mice strains that are both defective in CD95/CD95L signaling [36]. This indicates that AICD may not be impaired by FLIP S overexpression in vivo.…”

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confidence: 93%

Transgenic overexpression of the Caspase‐8 inhibitor FLIP_short leads to impaired T cell proliferation and an increased memory T cell pool after staphylococcal enterotoxin B injection

et al. 2005

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The cellular homologues of the viral anti-apoptotic v-FLIP proteins exist as a long (c-FLIP L ) and a short (c-FLIP S ) splice variant. While c-FLIP S and v-FLIP are composed solely of two death effector domains, c-FLIP L contains an (inactive) caspase-like domain in addition to these two death effector domains, thereby structurally resembling proCaspase-8. Both c-FLIP L and c-FLIP S suppress apoptosis by inhibiting Caspase-8 activation, although at different levels of pro-Caspase-8 processing. To analyze the consequences of deregulated c-FLIP S expression in vivo, we established lck FLIP Stransgenic mice overexpressing the transgene in thymocytes and in mature T cells. As expected, CD95L-induced apoptosis was impaired in lck FLIP S -transgenic T cells, indicating the functionality of the FLIP S transgene. Remarkably, activation-induced cell death of transgenic T cells was unaffected, despite the observed inhibition of CD95-induced T cell death. Thymic and splenic cell numbers as well as CD4/CD8 cellularity were normal in lck FLIP S -transgenic animals, which in contrast to CD95-deficient mice do not accumulate Thy1 + B220 + CD4 -CD8 -peripheral T cells. c-FLIP S overexpression leads to a significant decrease in activation-induced T cell proliferation in vitro. Despite the capacity of FLIP S to inhibit CD95-induced apoptosis, T cell lymphomagenesis is not observed in lck FLIP S -transgenic mice. Interestingly, the Vb8 + memory T cell pool is enlarged upon staphylococcal enterotoxin B injections, suggesting a specific in vivo function for FLIP S in the maintenance of restimulated T cells. IntroductionAmong many anti-apoptotic regulatory proteins, the Caspase-8-inhibitory FLIP molecule has been studied intensively. Originally detected in different viruses, c-FLIP was eventually identified as the cellular homologue of the v-FLIP proteins ([1, 2] and references herein). Several spliced isoforms of c-FLIP have been characterized, two of which are expressed as proteins: c-FLIP L , the full-length 55-kDa form of c-FLIP, comprises two Nterminal death effector domains (DED) and an enzymatically inactive caspase domain, thereby structurally resembling . c-FLIP S is a shorter 26-kDa form of c-FLIP and, like v-FLIP, contains only the two DED.A functional pro-apoptotic death-inducing signaling complex (DISC) is usually assembled by recruitment of the adaptor protein FADD to the activated CD95 receptor via death domain interactions [3]. Due to binding of their DED, FADD then associates Caspase-8 Molecular immunologyThe first two authors contributed equally to this work. [2,5]. Recruitment of both c-FLIP L and c-FLIP S to the activated intracellular CD95 receptor complex by FADD has been demonstrated, and both proteins are able to inhibit CD95-induced apoptosis as well as cell death mediated by other death receptors [6]. It has even been suggested that c-FLIP S rather than c-FLIP L may be the prime inhibitor of CD95-mediated apoptosis in T cells [7]. Nevertheless, a recent study showed that whereas high levels of c-FLIP L o...

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Fas and Fas ligand: lpr and gld mutations

Cited by 840 publications

References 45 publications

TRAIL and immunity: more than a license to kill tumor cells

TRAIL and immunity: more than a license to kill tumor cells

Involvement of Fas (CD95/APO-1) and Fas ligand in apoptosis induced by ganciclovir treatment of tumor cells transduced with herpes simplex virus thymidine kinase

Transgenic overexpression of the Caspase‐8 inhibitor FLIP_short leads to impaired T cell proliferation and an increased memory T cell pool after staphylococcal enterotoxin B injection

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Fas and Fas ligand: lpr and gld mutations

Cited by 840 publications

References 45 publications

TRAIL and immunity: more than a license to kill tumor cells

TRAIL and immunity: more than a license to kill tumor cells

Involvement of Fas (CD95/APO-1) and Fas ligand in apoptosis induced by ganciclovir treatment of tumor cells transduced with herpes simplex virus thymidine kinase

Transgenic overexpression of the Caspase‐8 inhibitor FLIPshort leads to impaired T cell proliferation and an increased memory T cell pool after staphylococcal enterotoxin B injection

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Transgenic overexpression of the Caspase‐8 inhibitor FLIP_short leads to impaired T cell proliferation and an increased memory T cell pool after staphylococcal enterotoxin B injection