Modulation of T-cell responses to alloantigens by TR6/DcR3

Zhang, Jun; Salcedo, Theodora W.; Wan, Xiaochun; Ullrich, Stephen J.; Hu, Bugen; Gregorio, Theresa; Feng, Ping; Qi, Shijie; Chen, Huifang; Cho, Yun Hee; Li, Yuling; Moore, Paul A.; Wu, Jiangping

doi:10.1172/jci12159

Cited by 107 publications

(125 citation statements)

References 34 publications

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“…Cytotoxic T-cell Assay-The assay was performed as detailed earlier using spleen cells from TCR transgenic 2C mice (19 (20). Because of such a high frequency of L d -specific precursors, this assay has high sensitivity and a high signal versus noise ratio and was routinely used to assess CTL activity in our laboratory (17,19,21).…”

Section: Methodsmentioning

confidence: 99%

“…Because of such a high frequency of L d -specific precursors, this assay has high sensitivity and a high signal versus noise ratio and was routinely used to assess CTL activity in our laboratory (17,19,21). 2C spleen cells (0.4 ϫ 10 6 cells/well) were stimulated with an equal amount of mitomycin C-treated BALB/c mouse spleen cells (H-2 d ) in flat-bottomed 96-well plates, which were pre-coated with EFNB1-Fc or normal human IgG (both at 10 g/ml).…”

Section: Methodsmentioning

confidence: 99%

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EphrinB1 Is Essential in T-cell-T-cell Co-operation during T-cell Activation

Luo

et al. 2004

Journal of Biological Chemistry

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Eph kinases are the largest family of receptor tyrosine kinases, and their ligands are ephrins (EFNs), which are also cell surface molecules. We have very limited knowledge about the expression and function of these kinases and their ligands in the immune system. In this study we investigated the effect of EFNB1 on mouse T-cells. EFNB1 and the Eph kinases it interacts with (collectively called EFNB1 receptors (EFNB1R)) were expressed on T-cells, B cells, and monocytes/macrophages. Some T-cells were double positive for EFNB1 and EFBB1R. Solid phase EFNB1 in the presence of suboptimal TCR ligation augmented T-cell responses in terms interferon-␥ secretion, proliferation, and cytotoxic T lymphocyte activity but not interleukin-2 production. After T-cell receptor (TCR) ligation, EFNB1R congregated to TCR caps, and then both of them translocated to raft caps. This provides a morphological basis for EFNB1R to enhance TCR signaling. Further downstream of the signaling pathway, EFNB1R stimulation led to increased LAT (linker for activation of T-cells) phosphorylation and p44/42 and p38 MAPK activation. Similar to CD28 costimulation, EFNB1R costimulation was insensitive to cyclosporin A inhibition. On the other hand, unlike the former, EFNB1R costimulation failed to activate Akt, which is essential in triggering interleukin-2 production. Our study suggests that EFNB1 is pivotal in T-cell-T-cell costimulation and in reducing T-cell response threshold to antigen stimulation.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

EphrinB1 Is Essential in T-cell-T-cell Co-operation during T-cell Activation

Luo

et al. 2004

Journal of Biological Chemistry

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“…2 It is a ligand for TR2/HVEM, LT␤R, and TR6/DcR3, all of which are TNF receptor (TNFR) family members. 1,3,4 Recent studies show that LIGHT can costimulate T-cell responses via TR2. 2,5,6 LIGHT can also induce apoptosis in cells expressing both TR2 and LT␤R, 7 although Rooney et al 8 reported that LT␤R is necessary and sufficient for LIGHT-mediated apoptosis in tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Mouse T cells receive costimulatory signals from LIGHT, a TNF family member

Shi

Luo

Wan

et al. 2002

Blood

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“…DcR3 regulates CD14 ϩ monocyte differentiation into dendritic cells, with down-regulation of HLA-DR, CD56/ICAM-1, and CD80, and up-regulation of CD86 in mature dendritic cells, leading to skewed Th2 differentiation in primed T cells (10). DcR3 attenuates T cell activation and reduces T cell response to mouse heart allograft (11). DcR3 also decreases T cell interaction with antigen-presenting cells (12) and inhibits T cell chemotaxis (13).…”

Section: Decoy Receptor 3 (Dcr3)mentioning

confidence: 99%

“…We thus used lymphotoxin ␤ receptor-Fc (LT␤R.Fc) to examine whether binding to Fc receptor would increase TRAIL-triggered apoptosis. In addition, LIGHT is a common ligand for LT␤R and DcR3 (2); binding to LIGHT has accounted for some of the biological activities of DcR3 (11,13). Jurkat T and U937 cells were incubated with TRAIL in the presence or absence of 10 g/ml LT␤R.Fc.…”

Section: Dcr3 Enhances Trail-induced Cellmentioning

confidence: 99%

Sensitization of Cells to TRAIL-induced Apoptosis by Decoy Receptor 3

Wu¹,

Chang

Hsu

et al. 2004

Journal of Biological Chemistry

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Decoy receptor 3 (DcR3)/TR6/M68 is a soluble receptor that binds to the Fas ligand LIGHT and TL1A. Elevated levels of DcR3 expression have been found in many tumors. We report an unexpected effect of DcR3 by sensitizing Jurkat and U937 cells to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Cell death triggered by anti-Fas and tumor necrosis factor was unaffected by DcR3. DcR3 by itself did not stimulate apoptosis. The ability to augment TRAIL-initiated cell death was not observed with soluble lymphotoxin ␤ receptor or soluble death receptor 3, indicating that binding to LIGHT or TL1A alone is insufficient to trigger TRAIL sensitivity. Incubation with DcR3 did not increase the surface expression of TRAIL receptor, and the level of Fas-associated death domain protein and cellular FLICE-like inhibitory protein was not altered. Instead, in the presence of DcR3, TRAIL engagement resulted in an increased activation of caspase-8, an elevated cleavage of Bid, and enhanced release of Smac and cytochrome c from mitochondria to cytosol compared with TRAIL alone. This led to increased activation of caspase-9 and caspase-3. The unusual ability of DcR3 to promote TRAIL-triggered death may be used to potentiate TRAIL efficacy during treatment tumors overexpressing DcR3. Decoy receptor 3 (DcR3)1 /TR6/M68 is a member of the tumor necrosis factor receptor superfamily (1). DcR3 binds to at least three different ligands: Fas ligand (FasL), LIGHT, and TL1A (1-3). The biological functions initiated by these three ligands are blocked by the presence of DcR3. DcR3 is overexpressed in primary lung and colon tumors (1), in gliomas (4), gastrointestinal tract tumors (5, 6), autoimmune tissues (7), and virusassociated leukemia (8). It has been suggested that DcR3 acts as a decoy receptor for tumor cells to neutralize the cytotoxic and regulatory effects of FasL, LIGHT, and TL1A, in that inoculation of rats with glioma cells overexpressing DcR3 resulted in decreased infiltration of T cells and macrophages (4).DcR3 has also been shown to promote angiogenesis through neutralization of TL1A (9).Recent studies have revealed the profound modulatory effects of DcR3 on many cells. DcR3 regulates CD14 ϩ monocyte differentiation into dendritic cells, with down-regulation of HLA-DR, CD56/ICAM-1, and CD80, and up-regulation of CD86 in mature dendritic cells, leading to skewed Th2 differentiation in primed T cells (10). DcR3 attenuates T cell activation and reduces T cell response to mouse heart allograft (11). DcR3 also decreases T cell interaction with antigen-presenting cells (12) and inhibits T cell chemotaxis (13). In addition, DcR3 triggers actin re-organization, increases the adhesion of monocytes (14), and reduces phagocytic activity and proinflammatory cytokine production in macrophages (15).TRAIL induces apoptosis by binding to TRAIL receptor (16, 17). There are five different TRAIL receptors, including TRAIL-R1/DR4, TRAIL-R2/DR5, TRAIL-R3/DcR1, TRAIL-R4/ DcR2, and osteoprotegerin. Binding of DR4 and DR...

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Modulation of T-cell responses to alloantigens by TR6/DcR3

Cited by 107 publications

References 34 publications

EphrinB1 Is Essential in T-cell-T-cell Co-operation during T-cell Activation

EphrinB1 Is Essential in T-cell-T-cell Co-operation during T-cell Activation

Mouse T cells receive costimulatory signals from LIGHT, a TNF family member

Sensitization of Cells to TRAIL-induced Apoptosis by Decoy Receptor 3

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