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Downregulation of CD95 in transformed cells may provide a means to evade clearance by effector lymphocytes. This study demonstrates that downregulation of CD95 expression can be mediated by Ras, thus providing evidence for a dual purpose of Ras: oncogenic transformation and immune avoidance.
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Peli J., Schroter M., Rudaz C., Hahne M., Meyer C., Reichmann E., Tschopp J. Oncogenic Ras inhibits Fas ligand-mediated apoptosis by downregulating the expression of Fas. EMBO J. 18:1999;1824-1831. Downregulation of CD95 in transformed cells may provide a means to evade clearance by effector lymphocytes. This study demonstrates that downregulation of CD95 expression can be mediated by Ras, thus providing evidence for a dual purpose of Ras: oncogenic transformation and immune avoidance.
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In an elegant study with localised activation of c-Myc in keratinocytes, this paper describes the ability to generate a pre-neoplastic lesion by forced activation of c-Myc - an effect that is transient and reversible when c-Myc is deactivated.
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An intriguing study showing the involvement of CD95L in shedding of skin following sunburn. This raises the possibility that sunburn and subsequent shedding of skin is a protective mechanism against skin cancer to remove damaged keratinocytes. A debate over the potential positive effects of sunburn versus sunscreen has ensued.
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Hill L.L., Ouhtit A., Loughlin S.M., Kripke M.L., Ananthaswamy H.N., Owen Schaub L.B. Fas ligand: a sensor for DNA damage critical in skin cancer etiology. Science. 285:1999;898-900. An intriguing study showing the involvement of CD95L in shedding of skin following sunburn. This raises the possibility that sunburn and subsequent shedding of skin is a protective mechanism against skin cancer to remove damaged keratinocytes. A debate over the potential positive effects of sunburn versus sunscreen has ensued.
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Hill, L.L.1
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The title pretty much says it all. A new molecule implicated in immune avoidance by inhibiting CD95-CD95L interactions. Expression of a novel decoy receptor, DcR3, by malignancies is seen as an effective means to avoid being removed by CD95-CD95L mediated immune surveillance.
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The first report of a caspase mutation associated with a human disease. It inludes interesting data showing the involvement of a dominant negative caspase-10 acting at the unlikely level of caspase-8.
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Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN
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This paper draws a link between the lack of PTEN phosphatase activity with an increase in protein kinase B activity and its association with glioblastoma. On the basis of the high incidence of PTEN mutations in glioblastoma and prostate cancers, the authors suggest that dysregulation of the PI3-kinase pathway is a major mediator of oncogenesis.
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The studies here demonstrate that lymphocytes activated in vivo have a higher propensity to undergo apoptosis in culture ex vivo and that reactive oxygen species appear to mediate this process. The authors propose that this is a physiologically relevant mediator of AICD that is driven by elevated levels of ROS in active lymphocytes because of their heightened metabolic state.
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Hildeman, D.A.1
Mitchell, T.2
Teague, T.K.3
Henson, P.4
Day, B.J.5
Kappler, J.6
Marrack, P.C.7
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39
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17944394558
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Inducible nonlymphoid expression of Fas ligand is responsible for superantigen-induced peripheral deletion of T cells
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This paper is the first demonstration that inducible CD95L expression by non-lymphoid tissue assists in the removal of activated peripheral lymphocytes, giving rise to the notion of 'inducible immune privilege' and its contribution to peripheral deletion.
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Bonfoco E., Stuart P.M., Brunner T., Lin T., Griffith T.S., Gao Y., Nakajima H., Henkart P.A., Ferguson T.A., Green D.R. Inducible nonlymphoid expression of Fas ligand is responsible for superantigen-induced peripheral deletion of T cells. Immunity. 9:1998;711-720. This paper is the first demonstration that inducible CD95L expression by non-lymphoid tissue assists in the removal of activated peripheral lymphocytes, giving rise to the notion of 'inducible immune privilege' and its contribution to peripheral deletion.
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(1998)
Immunity
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Bonfoco, E.1
Stuart, P.M.2
Brunner, T.3
Lin, T.4
Griffith, T.S.5
Gao, Y.6
Nakajima, H.7
Henkart, P.A.8
Ferguson, T.A.9
Green, D.R.10
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41
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0030951069
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A vision of cell death: Insights into immune privilege
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Ferguson T.A., Griffith T.S. A vision of cell death: insights into immune privilege. Immunol Rev. 156:1997;167-184.
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Immunol Rev
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Ferguson, T.A.1
Griffith, T.S.2
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42
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0032573581
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Regulation of the proinflammatory effects of Fas ligand (CD95L)
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This is an intriguing study showing that CD95L contributes to a pro-inflammatory response by transplanted cells and that these effects are moderated in the presence of TGF-β. It is not surprising that CD95L does not always guarantee survival of a transplanted graft and these studies show that TGF-β (and conceivably other cytokines as well) given at the site of transplant may improve success of a graft.
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Chen J.J., Sun Y., Nabel G.J. Regulation of the proinflammatory effects of Fas ligand (CD95L). Science. 282:1998;1714-1717. This is an intriguing study showing that CD95L contributes to a pro-inflammatory response by transplanted cells and that these effects are moderated in the presence of TGF-β. It is not surprising that CD95L does not always guarantee survival of a transplanted graft and these studies show that TGF-β (and conceivably other cytokines as well) given at the site of transplant may improve success of a graft.
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(1998)
Science
, vol.282
, pp. 1714-1717
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Chen, J.J.1
Sun, Y.2
Nabel, G.J.3
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43
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0030972396
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Transgenic expression of CD95 ligand on islet beta cells induces a granulocytic infiltration but does not confer immune privilege upon islet allografts
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Allison J., Georgiou H.M., Strasser A., Vaux D.L. Transgenic expression of CD95 ligand on islet beta cells induces a granulocytic infiltration but does not confer immune privilege upon islet allografts. Proc Natl Acad Sci USA. 94:1997;3943-3947.
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Proc Natl Acad Sci USA
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Allison, J.1
Georgiou, H.M.2
Strasser, A.3
Vaux, D.L.4
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44
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0032961753
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Accelerated rejection of Fas ligand-expressing heart grafts
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Takeuchi T., Ueki T., Nishimatsu H., Kajiwara T., Ishida T., Jishage K., Ueda O., Suzuki H., Li B., Moriyama N., Kitamura T. Accelerated rejection of Fas ligand-expressing heart grafts. J Immunol. 162:1999;518-522.
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J Immunol
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Takeuchi, T.1
Ueki, T.2
Nishimatsu, H.3
Kajiwara, T.4
Ishida, T.5
Jishage, K.6
Ueda, O.7
Suzuki, H.8
Li, B.9
Moriyama, N.10
Kitamura, T.11
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45
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0030680119
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Immune response and myoblasts that express Fas ligand
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Kang S.M., Hoffmann A., Le D., Springer M.L., Stock P.G., Blau H.M. Immune response and myoblasts that express Fas ligand. Science. 278:1997;1322-1324.
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Science
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Kang, S.M.1
Hoffmann, A.2
Le, D.3
Springer, M.L.4
Stock, P.G.5
Blau, H.M.6
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46
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0032494144
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Antiinflammatory effects of CD95 ligand (FasL)-induced apoptosis
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These studies outline some of the requirements for CD95L to maintain immune privilege status by virtue of differential cytokine expression. Notably, IL10 production by apoptotic cells resulted in the skewing of neighbouring lymphocytes to the anti-inflammatory Th2 subtypes, whereas in the absence of IL10, the Th1 subset was favoured with potentially inflammatory effects.
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Gao Y., Herndon J.M., Zhang H., Griffith T.S., Ferguson T.A. Antiinflammatory effects of CD95 ligand (FasL)-induced apoptosis. J Exp Med. 188:1998;887-896. These studies outline some of the requirements for CD95L to maintain immune privilege status by virtue of differential cytokine expression. Notably, IL10 production by apoptotic cells resulted in the skewing of neighbouring lymphocytes to the anti-inflammatory Th2 subtypes, whereas in the absence of IL10, the Th1 subset was favoured with potentially inflammatory effects.
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(1998)
J Exp Med
, vol.188
, pp. 887-896
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Gao, Y.1
Herndon, J.M.2
Zhang, H.3
Griffith, T.S.4
Ferguson, T.A.5
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47
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0031938030
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Downregulation of Fas ligand by shedding
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The authors present a model to explain the protection of bystander cells in the vicinity of activated cytotoxic lymphocytes, in which soluble CD95L is produced by the CTL. In this model, only cells making physical contact with membrane bound CD95L on the CTL would be deleted.
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Tanaka M., Itai T., Adachi M., Nagata S. Downregulation of Fas ligand by shedding. Nat Med. 4:1998;31-36. The authors present a model to explain the protection of bystander cells in the vicinity of activated cytotoxic lymphocytes, in which soluble CD95L is produced by the CTL. In this model, only cells making physical contact with membrane bound CD95L on the CTL would be deleted.
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(1998)
Nat Med
, vol.4
, pp. 31-36
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Tanaka, M.1
Itai, T.2
Adachi, M.3
Nagata, S.4
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48
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0032550366
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Conversion of membrane-bound Fas(CD95) ligand to its soluble form is associated with downregulation of its proapoptotic activity and loss of liver toxicity
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Schneider P., Holler N., Bodmer J.L., Hahne M., Frei K., Fontana A., Tschopp J. Conversion of membrane-bound Fas(CD95) ligand to its soluble form is associated with downregulation of its proapoptotic activity and loss of liver toxicity. J Exp Med. 187:1998;1205-1213.
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(1998)
J Exp Med
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, pp. 1205-1213
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Schneider, P.1
Holler, N.2
Bodmer, J.L.3
Hahne, M.4
Frei, K.5
Fontana, A.6
Tschopp, J.7
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49
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0031740779
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Fas ligand is present in tumors of the Ewing's sarcoma family and is cleaved into a soluble form by a metalloproteinase
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Mitsiades N., Poulaki V., Kotoula V., Leone A., Tsokos M. Fas ligand is present in tumors of the Ewing's sarcoma family and is cleaved into a soluble form by a metalloproteinase. Am J Pathol. 153:1998;1947-1956.
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Am J Pathol
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Mitsiades, N.1
Poulaki, V.2
Kotoula, V.3
Leone, A.4
Tsokos, M.5
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50
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0033559492
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Soluble Fas ligand is chemotactic for human neutrophilic polymorphonuclear leukocytes
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The findings in these studies support the notion of a pro-inflammatory effect of CD95L. The authors demonstrate that soluble CD95L can attract neutrophils which contributes to inflammation. This finding provides insights into a possible mechanism to explain earlier observations that CD95L-bearing grafts may mediate rejection.
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Ottonello L., Tortolina G., Amelotti M., Dallegri F. Soluble Fas ligand is chemotactic for human neutrophilic polymorphonuclear leukocytes. J Immunol. 162:1999;3601-3606. The findings in these studies support the notion of a pro-inflammatory effect of CD95L. The authors demonstrate that soluble CD95L can attract neutrophils which contributes to inflammation. This finding provides insights into a possible mechanism to explain earlier observations that CD95L-bearing grafts may mediate rejection.
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(1999)
J Immunol
, vol.162
, pp. 3601-3606
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Ottonello, L.1
Tortolina, G.2
Amelotti, M.3
Dallegri, F.4
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51
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0029788696
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Differential expression of Fas (CD95) and Fas ligand on normal human phagocytes: Implications for the regulation of apoptosis in neutrophils
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Liles W.C., Kiener P.A., Ledbetter J.A., Aruffo A., Klebanoff S.J. Differential expression of Fas (CD95) and Fas ligand on normal human phagocytes: implications for the regulation of apoptosis in neutrophils. J Exp Med. 184:1996;429-440.
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J Exp Med
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Liles, W.C.1
Kiener, P.A.2
Ledbetter, J.A.3
Aruffo, A.4
Klebanoff, S.J.5
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