ライフサイエンスコーパス: CD95L

1 CD95L expression markedly reduced allogeneic cytotoxic T

2 CD95L expression on epithelium of full-thickness cornea

3 CD95L was detected in tumors in vivo at levels up to 10(

4 Much of what we know about CD95L-dependent killing is in fact bystander killing bec

5 ation of wortmannin and blocking mAb against CD95L inhibited the cytolysis of CD95+ targets, indicati

6 ator of NF-kappaB ligand (RANKL), TNF-alpha, CD95L, and TNF-related apoptosis inducing ligand (TRAIL)

7 ression of functional Fas ligand (FasL, also CD95L) on the injected bone marrow cells is required for

8 Although CD95L contributes to immune privilege in the cornea and

9 Although CD95L is required for T cell receptor (TCR)-induced cell

10 l or cauterized eyes of BALB/c, C57BL/6, and CD95L-deficient B6-gld mice were grafted beneath the kid

11 inducing ligands that includes TNF-alpha and CD95L (FasL).

12 uggesting a regulatory link between CD28 and CD95L expression.

13 nervous system, and that functional CD95 and CD95L are important for the progression of clinical dise

14 ted via TCR plus IL-2, up-regulated CD95 and CD95L expression (p < 0.001) and suppressed CD8(+) RC pr

15 d lpr or gld mice and attributed to CD95 and CD95L gene mutations, respectively.

16 tudy, we investigated expression of CD95 and CD95L in 11 patients with CD3(+) LGL leukemia and explor

17 esting 4666 shRNAs derived from the CD95 and CD95L mRNA sequences and an unrelated control gene, Venu

18 Mutations of CD95 and CD95L, lpr and gld, respectively, are associated with sp

19 sociated with de novo expression of CD95 and CD95L, suggesting that 9NC-induced apoptosis is mediated

20 We infected CD95- and CD95L-deficient mice (lpr and gld, respectively) with LC

21 The interaction between CD95 (Fas) and CD95L (Fas ligand) initiates apoptosis in a variety of c

22 st difference between perforin/granzyme- and CD95L/CD95-dependent cytolysis.

23 granzyme A and B, granulysin, perforin, and CD95L (Fas ligand).

24 , IFN-gamma, proopiomelanocortin (POMC), and CD95L (Fas L).

25 In fact, anti-CD95L mAb inhibited partially (50%) T cell-mediated XS52

26 of liver cell apoptosis using membrane-bound CD95L as the inducing agent.

27 idence of apoptosis caused by membrane-bound CD95L differs from the much smaller effects induced by t

28 CD95L was caused by neutrophils activated by CD95L.

29 model for CD95-mediated apoptosis induced by CD95L.

30 licated caspase-10 in apoptosis signaling by CD95L and Apo2L/TRAIL, recent studies indicated that the

31 death mediator Fas ligand (FasL, also called CD95L) in the vasculature of human and mouse solid tumor

32 ntransfected cells expressing both caspases, CD95L and Apo2L/TRAIL recruited endogenous caspase-10 as

33 ess multiple activation markers (circa CD69, CD95L, CD122, and LFA-1) and contain IL-2 and IFN-gamma

34 levels of the physiological ligand for CD95, CD95L.

35 Thus, perforin and CD95-CD95L were not involved in CD4(+) and CD8(+) T cell medi

36 cally deficient mice revealed that host CD95-CD95L function did not alter tumor growth, demonstrating

37 tivated T cells through Fas-Fas ligand (CD95-CD95L) interactions is one mechanism of peripheral self-

38 Ab blockade of the CD95-CD95L interaction decreased cytolytic function for both

39 r, inhibition of perforin activity, the CD95-CD95L interaction, or both CTL mechanisms did not affect

40 effect, 9NC can additionally activate a CD95/CD95L-dependent apoptotic pathway.

41 Defects in CD95/CD95L (Fas-Ligand)-apoptotic pathway have been recognize

42 Examples include CD95/CD95L acting as cytotoxic CD8+ T cell effector molecules

43 expressed constitutively high levels of CD95/CD95L, similar to those seen in normal activated T cells

44 The CD95/CD95L pair plays a manifold role in regulating life and

45 diated by the perforin/granzyme and the CD95/CD95L system.

46 Metalloprotease-cleaved CD95L (cl-CD95L) is released into the bloodstream but does not tri

47 expressed CD95L and that after cleavage, cl-CD95L promoted T helper 17 (Th17) lymphocyte transmigrat

48 Hence, the pathophysiological role of cl-CD95L remains unclear.

49 Th17 cells stimulated with cl-CD95L produced sphingosine-1-phosphate (S1P), which prom

50 Metalloprotease-cleaved CD95L (cl-CD95L) is released into the bloodstream but do

51 astatic function for metalloprotease-cleaved CD95L in TNBCs, revisiting its role in carcinogenesis.

52 By contrast, CD95L/FASL was expressed in only 3 (12%) of 26 ALCL tumo

53 CT26-CD95L survived in the intraocular space because of the p

54 transfected colon carcinoma cell line, CT26-CD95L, the molecular basis for these divergent responses

55 n injected subcutaneously, rejection of CT26-CD95L was caused by neutrophils activated by CD95L.

56 ttractant effect of endothelial cell-derived CD95L in induction of neutrophil recruitment and support

57 nor IFN-gamma-treated EC express detectable CD95L mRNA or protein.

58 n untreated psoriatic plaques do not express CD95L on their plasma membrane, after UV-B treatment the

59 We provide evidence that thymocytes express CD95L/luciferase after strong TCR ligation and that indu

60 Keratinocytes induced to express CD95L acquired the functional capacity to kill a CD95-po

61 minimal apoptosis when transduced to express CD95L.

62 -2 or IL-12, and could be induced to express CD95L.

63 ulting "killer" DC-DC hybrids: (1) expressed CD95L and MHC class I and class II molecules of both A/J

64 lupus erythematosus (SLE) patients expressed CD95L and that after cleavage, cl-CD95L promoted T helpe

65 but only Treg from cancer patients expressed CD95L.

66 asts, stably transfected with mouse CD95L (F(CD95L+)).

67 lasts stably transfected with vector only (F(CD95L-)) served as controls.

68 en normal hepatocytes were cocultured with F(CD95L+) and were not observed with F(CD95L-) or in hepat

69 e that coculture of mouse hepatocytes with F(CD95L+) is a useful in vitro model for CD95-mediated apo

70 with F(CD95L+) and were not observed with F(CD95L-) or in hepatocytes from Fas(lpr) mice.

71 ed both perforin- and Fas ligand (FasL)/Fas (CD95L/CD95)-mediated cytolytic mechanisms, SEB was unabl

72 clones appears to be restricted to FasL/Fas (CD95L/CD95) mediated cytolysis.

73 C57BL/6(B6), FasL (CD95L)-deficient B6-gld, and Fas (CD95)-deficient B6-lpr

74 phage CSF + IL-4 were found to express FasL (CD95L) mRNA by reverse transcriptase PCR and to uniforml

75 The binding of FasL (CD95L) to its receptor, Fas (CD95), induces apoptosis.

76 fector molecules perforin (PFP) and/or FasL (CD95L) were necessary for CD4 T cell-mediated rejection

77 aluate the effects of IL-4 in Fas(CD95)/FasL(CD95L)-mediated killing of Fas-overexpressing target cel

78 ducing signal triggered by Fas ligand (FasL, CD95L) and TNF.

79 Fas ligand (FasL, CD95L) expression helps control inflammatory reactions i

80 Fas ligand (FasL/CD95L) is best known for its role in delivering apoptoti

81 Fas ligand (FasL/CD95L), a member of the tumor necrosis factor family, in

82 ntry mediator (HVEM)-L) and Fas ligand (FasL/CD95L).

83 Fas ligand (FasL/CD95L/APO-1L) is one of a growing number of TNF family m

84 ion between Fas (CD95) and its ligand (FasL; CD95L) has been shown to be involved in mediating apopto

85 Fas (CD95), by its ligand, Fas ligand (FasL; CD95L), among other mechanisms.

86 ecules by help of highly active hexameric Fc-CD95L or membrane CD95L.

87 For CD95L-positive G209-specific CTL, the sensitization was

88 The cytotoxicity of supernatants from CD95L-expressing cells was increased by incubation on ti

89 eficient mice and in mice lacking functional CD95L, excluded a direct role for either cytotoxic T lym

90 orneas from eyes of C57BL/6 (B6) and B6.gld (CD95L deficient) mice were (1) rendered into small full-

91 In the latter type of corneal grafts, CD95L expression on the endothelium plays an essential r

92 otic status (c-FLIP(short)(low), CD95(high), CD95L(high)).

93 Of interest, both extrinsic apoptosis in CD95L-treated CD10- B cells and intrinsic apoptosis in C

94 transcriptional regulatory role for CD28 in CD95L-mediated functional activity in CD4+ T cells.

95 of CD95 are similar to observations made in CD95L transgenic mice.

96 Cultured mouse I/CB PE cells (including CD95L-deficient cells), which were more than 95% keratin

97 ntrast, W did not inhibit the Ag/MHC-induced CD95L expression or the CD95L/CD95-mediated cytolysis of

98 after strong TCR ligation and that inducible CD95L promoter activation is present, but unequal, in bo

99 the Fc domain of an IgG1 antibody inhibited CD95L-induced apoptosis without interfering with T-cell

100 Such immunological events involving CD95L provide new insight and opportunity for novel trea

101 ent there is strong and diffuse keratinocyte CD95L expression that coincided in a temporal fashion wi

102 for UV-B light in psoriasis via keratinocyte CD95L expression.

103 gram in cells upon binding either its ligand CD95L or antibody.

104 investigated the effect of Fas/APO1-ligand (CD95L) gene transfer on allogeneic immune responses in v

105 of CD95 (Fas) by XS52 DC and of CD95 ligand (CD95L) (Fas ligand) by activated HDK-1 T cells, suggesti

106 we report that serum levels of CD95 ligand (CD95L) are higher in patients with TNBC than in other pa

107 t DCs that are transfected with CD95 ligand (CD95L) cDNA, called 'killer' DCs, deliver death signals,

108 As and shRNAs targeting CD95 or CD95 ligand (CD95L) induce a form of cell death characterized by simu

109 CD95 ligand (CD95L) is expressed by immune cells and triggers apoptot

110 Here we describe high extrinsic CD95 ligand (CD95L)-mediated apoptosis in CD10-/CD21lo mature/activat

111 n/granzyme- and Fas ligand/Fas (CD95 ligand (CD95L)/CD95)-mediated pathways.

112 btained from eyes of normal and CD95 ligand (CD95L)deficient mice and tested for their capacity to su

113 transmigration upon binding of CD95-ligand (CD95L) that is presented by endothelial cells.

114 therefore potential targets for CD95-ligand (CD95L)-mediated injury.

115 Fas (CD95) and Fas ligand (CD95L) are an interacting receptor-ligand pair required

116 transcription and expression of Fas ligand (CD95L) in T cell lines, suggesting a regulatory link bet

117 Fas ligand (CD95L) inhibits T cell function in immune-privileged org

118 Fas ligand (CD95L) is synthesized both on the cell surface membrane

119 ) strongly and diffusely express Fas ligand (CD95L), but not Fas antigen (CD95).

120 w levels of Fas, suggesting that Fas ligand (CD95L)-mediated target cell lysis was occurring in vivo.

121 tact-dependent manner, involving Fas-ligand (CD95L).

122 ever, the elimination of CD95 or its ligand, CD95L, from cancer cells results in death induced by CD9

123 otic status (c-FLIP(short)(high), CD95(low), CD95L(low)) toward a proapoptotic status (c-FLIP(short)(

124 However, when Gaussia princeps luciferase-CD95L trimers were used as tracers to "mark" inactive CD

125 We demonstrate that maximal CD95L promoter activity occurs only after prolonged T ce

126 highly active hexameric Fc-CD95L or membrane CD95L.

127 In normal mice, CD95L-expressing endothelium can inhibit the stroma from

128 ponse, the same stimulus induces only modest CD95L promoter activity.

129 Moreover, CD95L can be induced on normal cultured keratinocytes af

130 Moreover, CD95L expressed on stroma-endothelium grafts protected e

131 bly transfected with a vector encoding mouse CD95L and was inoculated into C57BL/6 mice.

132 3 fibroblasts, stably transfected with mouse CD95L (F(CD95L+)).

133 ic mouse strain, CD95LP-Luc, in which murine CD95L promoter sequence controls the expression of a luc

134 If stroma-endothelium grafts had no CD95L expression, DH directed against major histocompati

135 r did they induce DH unless the graft had no CD95L expression.

136 tual frameworks for clinical applications of CD95L-transduced killer hybrids created between donor DC

137 Metalloprotease-mediated cleavage of CD95L expressed by endothelial cells surrounding tumors

138 In contrast, deletion of CD95L in peripheral myeloid cells significantly protects

139 e mechanism for CD28-mediated enhancement of CD95L.

140 ivity correlates with enhanced expression of CD95L mRNA, cell surface expression of CD95L protein, an

141 Strikingly, expression of CD95L on these allogeneic tumors completely inhibited th

142 on of CD95L mRNA, cell surface expression of CD95L protein, and increased apoptosis of CD95+ target c

143 of them located in the open reading frame of CD95L.

144 study, knowledge related to the induction of CD95L promoter activity in primary T cells is lacking.

145 This induction of CD95L was confirmed at the mRNA and protein levels using

146 Systemic pharmacological inhibition of CD95L dampens the peripheral innate response, reduces th

147 The localization of CD95L in different cell types within tumors has not been

148 ter domain, we found that oligomerization of CD95L has no major effect on CD95 occupancy.

149 Although the regulation of CD95L expression on activated T cells is an area of inte

150 ngs related to transcriptional regulation of CD95L in primary T cells.

151 ese results provide insight into the role of CD95L in regulating the alloantibody response and the ge

152 Treatment of CD95L-transduced cells with IFN-gamma causes apoptosis w

153 tes that the higher activity of oligomerized CD95L trimers is not related to an avidity-related incre

154 ced signaling pathway did not induce CD95 or CD95L expression.

155 studies using ubiquitous deletion of CD95 or CD95L in mouse models of neurodegeneration have generate

156 on using tissue-specific deletion of CD95 or CD95L.

157 ivity of CD95, stimulated by cancer-produced CD95L, for optimal growth.

158 zing a N-terminal epitope tag in recombinant CD95L variants or by genetic engineering-enforced format

159 nd accurate binding studies with recombinant CD95L variants equipped with a Gaussia princeps lucifera

160 rts suggest that the cytotoxicity of soluble CD95L is insignificant, whereas others show potent respo

161 The retention of soluble CD95L on extracellular matrices is likely to play an imp

162 The capability of soluble CD95L trimers to trigger CD95-associated signaling pathw

163 Furthermore, binding of soluble CD95L trimers was found to be insufficient to increase t

164 timated the subunit stoichiometry of soluble CD95L using GFP fusion proteins.

165 analysis of the cornea revealed that soluble CD95L binds primarily to extracellular matrix.

166 this effect was mediated by trimeric soluble CD95L.

167 llular matrix proteins interact with soluble CD95L and potentiate its pro-apoptotic activity.

168 In this study, CD95L expression and its contribution to tumor growth ar

169 d not alter tumor growth, demonstrating that CD95L alone does not affect tumor growth.

170 se of immunoprecipitation, it was found that CD95L binds directly to fibronectin.

171 Our results indicate that CD95L is not an instrumental component of immune privile

172 We have previously reported that CD95L expression requires both protein kinase C (PKC) tr

173 hepatocytes towards CD95L we speculate that CD95L-induced liver damage in vivo may be minimized by r

174 Our data suggest that CD95L, which is found elevated in many human cancer pati

175 Mutational analysis of the CD95L promoter also reveals a novel transcriptional repr

176 basis for structure/function analysis of the CD95L promoter to elucidate the mechanism for CD28-media

177 t the Ag/MHC-induced CD95L expression or the CD95L/CD95-mediated cytolysis of CD95+ targets.

178 ite, that confers CD28 responsiveness to the CD95L gene.

179 This CD95L expression in vivo by BCC tumor cells is associate

180 Thus, CD95L inhibited alloantibody production and conferred lo

181 h as the eye and testis, yet in most tissues CD95L expression induces potent inflammatory responses.

182 Importantly, it forms independently of TNF, CD95L/FASL, TRAIL, death-receptors, and mitochondrial pa

183 ells with a neutralizing antibody (NOK-1) to CD95L or transient transfection of a c-FLIP(short) expre

184 wortmannin-independent cytolysis was due to CD95L/CD95 mediated cytolysis.

185 -gamma induces sensitivity of endothelium to CD95L-mediated apoptosis, and that this response may res

186 triggered migration of TNBC cells exposed to CD95L.

187 ed by restricting exposure of hepatocytes to CD95L.

188 sion of CD95 in HUVEC confers sensitivity to CD95L in the absence of IFN-gamma-treatment.

189 the high sensitivity of hepatocytes towards CD95L we speculate that CD95L-induced liver damage in vi

190 of aggregation of initially formed trimeric CD95L-CD95 complexes in CD95 activation.

191 ed survival between 60% and 100% if GVHD was CD95L mediated.

192 were induced in CD10+ B cells compared with CD95L-treated CD10- B cells, consistent with the greater

193 Thus, ligation of CD95 (on DC) with CD95L (on T cells) is one, but not the only, mechanism b

194 rgo CD95-initiated apoptosis when mixed with CD95L-transduced HUVEC or when incubated with pharmacolo

195 S106 (A/J mouse origin) was transfected with CD95L cDNA and fused with splenic DCs purified from allo