Cell-mediated cytotoxic mechanisms

Squier, Margaret; Cohen, John

doi:10.1016/0952-7915(94)90126-0

Cited by 42 publications

(12 citation statements)

References 24 publications

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“…In contrast, NK-depleted splenocytes, cultured at the same E : T ratio (2 : 1) or even at 5 : 1 (data not shown), failed to induce apoptosis. Mammalian NK cells are known to kill their targets by inducing apoptosis, a process initiated either through contact-mediated membrane signaling [e. g. Fas ligand/Fas interaction, CD40 ligand/CD40 interaction] or on the exocytosis of cytotoxic materials by the NK cell [23,24]. The mechanism of NK-induced apoptosis in Xenopus will be of interest to elucidate and may well involve Fas ligand/Fas interactions as a Faslike molecule has recently been identified on Xenopus lymphocytes [25].…”

Section: Discussionmentioning

confidence: 99%

Xenopus NK cells identified by novel monoclonal antibodies

et al. 2000

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Section: Discussionmentioning

confidence: 99%

Xenopus NK cells identified by novel monoclonal antibodies

et al. 2000

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“…The two primary functions of the FasR-FasL system are the maintenance of homeostasis in the immune system and the elimination of antigen-expressing target cells by cytotoxic T lymphocytes. [13][14][15] Binding of death ligands to DD-containing receptors initiates a common apoptotic pathway that involves aggregation of the receptors, which in turn causes the phosphorylation of amino acids in the DD. Phosphorylated DDs are recognized and bound by DD-containing adaptor proteins such as Fas-associated DD (FADD) and TNF-associated DD (TRADD).…”

mentioning

confidence: 99%

Enhanced apoptosis of glioma cell lines is achieved by co-delivering FasL-GFP and TRAIL with a complex Ad5 vector

Rubinchik

Woraratanadharm

et al. 2003

Cancer Gene Ther

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Brain tumors (BTs) are among the most malignant forms of human cancer. Unfortunately, current treatments are often ineffective and produce severe side effects. Cytotoxic gene therapy is an alternative treatment strategy, with the potential advantages of reduced toxicity to normal brain tissue. Apoptosis-inducing ''death ligands'' Fas ligand and TNF-related apoptosis-inducing ligand (TRAIL) are genes with substantial cytotoxic activity in susceptible tumor cells. Here, we compared the effectiveness of Ad vectormediated delivery of Fas ligand-green fluorescent protein (FasL-GFP) fusion protein, human TRAIL, and both genes simultaneously. We examined a panel of 13 cell lines (eight derived from primary isolates) for susceptibility to Ad5-based vector infection and for sensitivity to FasL-and TRAIL-mediated apoptosis. All cell lines were efficiently transduced, but, as expected, varied in their sensitivity to ligand-induced apoptosis. Generally, sensitivity to FasL-GFP correlated with cell surface FasR levels, but no such correlation was seen for TRAIL and its functional receptors, DR4 and DR5. The vector expressing both FasL-GFP and TRAIL was more effective than either of the single-gene vectors at comparable transduction levels, and it was effective against a broader range of cell lines. In five cell lines, coexpression resulted in apoptosis levels greater than those predicted for strictly additive activity of the two death ligands. We believe that Ad vector-mediated delivery of multiple death ligands may be developed as a potential BT therapy, either alone or in conjunction with surgical resection of the primary tumor.

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“…In short-term assays of cytolytic function, it was shown that perforin-dependent lysis was the most prominent mechanism, but that Fas ligand (Fas-L) 3 and TNF interactions could also bring about target death, albeit much less effectively (3). CD8 T cells have been shown to be effective in the elimination of tumors in a number of experimental models (reviewed in Ref.…”

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confidence: 99%

The Rate of the CD8-Dependent Initial Reduction in Tumor Volume Is Not Limited by Contact-Dependent Perforin, Fas Ligand, or TNF-Mediated Cytolysis

Hollenbaugh

Reome

Dobrzanski

et al. 2004

The Journal of Immunology

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Established EG7 tumors expressing OVA and growing at an intradermal site become rapidly reduced in size following adoptive therapy with in vitro-generated type I CD8 T cell (Tc1) effectors generated from naive CD8 T cells from transgenic TCR OVA-specific mice. Tc1 effectors kill EG7 target cells in vitro by a perforin-dependent mechanism. However, we show that there is no quantitative diminution of the initial phase of antitumor activity in vivo, whether the Tc1 effectors are derived from perforin-, Fas ligand-, or TNF-deficient transgenic TCR mice or whether the recipients are perforin deficient. Tumors are also equally well controlled whether the Tc1 effectors come from mice deficient in perforin plus Fas ligand or perforin plus TNF. Control of tumor growth is diminished when Tc1 effectors generated from IFN-γ-deficient mice are used. We conclude that control of tumor growth is not in any way affected by loss of contact-mediated lytic mechanisms, and conclude that the CD8 effectors must act by recruiting host effector mechanisms to control tumor growth.

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Cell-mediated cytotoxic mechanisms

Cited by 42 publications

References 24 publications

Xenopus NK cells identified by novel monoclonal antibodies

Xenopus NK cells identified by novel monoclonal antibodies

Enhanced apoptosis of glioma cell lines is achieved by co-delivering FasL-GFP and TRAIL with a complex Ad5 vector

The Rate of the CD8-Dependent Initial Reduction in Tumor Volume Is Not Limited by Contact-Dependent Perforin, Fas Ligand, or TNF-Mediated Cytolysis

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