Su1878 Tumor Necrosis Factor Receptor 2 Regulates Crosstalk Between CD8+ T Cells and the Gut Microbiome to Shape Distinct Microbial Milieu in Colitis

2016 ◽  
Vol 150 (4) ◽  
pp. S577-S578
Author(s):  
Shivesh Punit ◽  
Philip E. Dubé ◽  
Cambrian Y. Liu ◽  
Nandini Girish ◽  
Kay Washington ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Cd8 T Cells ◽  
Gut Microbiome ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Necrosis Factor

Antigen-primed CD8+ T cells can mediate resistance, preventing allogeneic marrow engraftment in the simultaneous absence of perforin-, CD95L-, TNFR1-, and TRAIL-dependent killing

Blood ◽  
2003 ◽  
Vol 101 (10) ◽  
pp. 3991-3999 ◽  
Author(s):  
Masanobu Komatsu ◽  
Michele Mammolenti ◽  
Monica Jones ◽  
Roland Jurecic ◽  
Thomas J. Sayers ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Cd8 T Cells ◽  
Barrier Function ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Proliferative Potential ◽  
Allogeneic Bone ◽  
Effector Pathways ◽  
Necrosis Factor

Abstract Engraftment failure following allogeneic bone marrow (BM) transplantation is of clinical concern particularly involving T-cell–depleted inoculum and transplantations for aplastic anemia. Immune resistance by lymphoid and natural killer (NK) populations with “barrier” function is well established. Major histocompatibility complex (MHC)–identical marrow allografts were examined to investigate effector pathways in non-NK–mediated resistance. Barrier function was examined in cytotoxic normal and deficient B6 (H-2b) recipients primed to donor minor histocompatibility antigen (MiHA) prior to BM transplantation. Host resistance was sensitively evaluated by colony-forming unit (CFU) assays to directly assess for donor progenitor cell (PC) and peripheral chimerism. B6 host CD8+ T cells but not CD4+ or NK1.1+ cells effected rejection of primitive (CFU-HPP [high-proliferative potential]) and lineage-committed (CFU-IL3/GM [interleukin 3/granulocyte macrophage]) allogeneic donor progenitors. To address complementation by the cytotoxic pathways existing in singly deficient (perforin or FasL) recipients, cytotoxically double (perforin plus FasL) deficient (cdd) recipients were used. Resistance in B6-cdd recipients was comparable to that of wild-type B6 recipients and was also dependent on CD8+ T cells. A “triple” cytotoxic deficient model, involving transplantation of TNFR1−/− (tumor necrosis factor receptor 1) progenitor grafts did not diminish the ability of B6-cdd recipients to reject allografts. Finally, injection of anti-TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) monoclonal antibody (mAb) in B6-cdd recipients also failed to inhibit rejection of TNFR1−/− marrow grafts. In total, these studies demonstrate that CD8+ host T cells can effectively resist MHC-matched MiHA-mismatched donor PCs via alternative effector pathway(s) independent of perforin-, FasL-, TNFR-1–, and TRAIL-dependent cytotoxicity. Therefore, inhibition of these effector pathways in sensitized recipients is unlikely to result in stem cell engraftment following PC allografts.

scholarly journals Enhanced efficacy and reduced toxicity of multifactorial adjuvants compared with unitary adjuvants as cancer vaccines

Blood ◽  
2008 ◽  
Vol 111 (6) ◽  
pp. 3116-3125 ◽  
Author(s):  
Cory L. Ahonen ◽  
Anna Wasiuk ◽  
Shinichiro Fuse ◽  
Mary Jo Turk ◽  
Marc S. Ernstoff ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Cancer Vaccine ◽  
Cd8 T Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Cell Mediated Immunity ◽  
Memory Cd8 T Cells ◽  
Immune Pathway ◽  
Necrosis Factor

Abstract Identification of Toll-like receptors (TLRs) and their ligands, and tumor necrosis factor–tumor necrosis factor receptor (TNF-TNFR) pairs have provided the first logical, hypothesis-based strategies to molecularly concoct adjuvants to elicit potent cell-mediated immunity via activation of innate and adaptive immunity. However, isolated activation of one immune pathway in the absence of others can be toxic, ineffective, and detrimental to long-term, protective immunity. Effective engineered vaccines must include agents that trigger multiple immunologic pathways. Here, we report that combinatorial use of CD40 and TLR agonists as a cancer vaccine, compared with monotherapy, elicits high frequencies of self-reactive CD8+ T cells, potent tumor-specific CD8+ memory, CD8+ T cells that efficiently infiltrate the tumor-burdened target organ; therapeutic efficacy; heightened ratios of CD8+ T cells to FoxP3+ cells at the tumor site; and reduced hepatotoxicity. These findings provide intelligent strategies for the formulation of multifactorial vaccines to achieve maximal efficacy in cancer vaccine trials in humans.

scholarly journals Tumor Necrosis Factor Receptor 2 Restricts the Pathogenicity of CD8+ T Cells in Mice With Colitis

2015 ◽  
Vol 149 (4) ◽  
pp. 993-1005.e2 ◽  
Author(s):  
Shivesh Punit ◽  
Philip E. Dubé ◽  
Cambrian Y. Liu ◽  
Nandini Girish ◽  
M. Kay Washington ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Cd8 T Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Necrosis Factor

scholarly journals GITR Activation Induces an Opposite Effect on Alloreactive CD4+ and CD8+ T Cells in Graft-Versus-Host Disease

2004 ◽  
Vol 200 (2) ◽  
pp. 149-157 ◽  
Author(s):  
Stephanie J. Muriglan ◽  
Teresa Ramirez-Montagut ◽  
Onder Alpdogan ◽  
Thomas W. van Huystee ◽  
Jeffrey M. Eng ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Graft Versus Host Disease ◽  
Cd8 T Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Allogeneic Bone ◽  
Host Disease ◽  
Graft Versus Host ◽  
Necrosis Factor

Glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) is a member of the tumor necrosis factor receptor (TNFR) family that is expressed at low levels on unstimulated T cells, B cells, and macrophages. Upon activation, CD4+ and CD8+ T cells up-regulate GITR expression, whereas immunoregulatory T cells constitutively express high levels of GITR. Here, we show that GITR may regulate alloreactive responses during graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). Using a BMT model with major histocompatibility complex class I and class II disparity, we demonstrate that GITR stimulation in vitro and in vivo enhances alloreactive CD8+CD25− T cell proliferation, whereas it decreases alloreactive CD4+CD25− proliferation. Allo-stimulated CD4+CD25− cells show increased apoptosis upon GITR stimulation that is dependent on the Fas–FasL pathway. Recipients of an allograft containing CD8+CD25− donor T cells had increased GVHD morbidity and mortality in the presence of GITR-activating antibody (Ab). Conversely, recipients of an allograft with CD4+CD25− T cells showed a significant decrease in GVHD when treated with a GITR-activating Ab. Our findings indicate that GITR has opposite effects on the regulation of alloreactive CD4+ and CD8+ T cells.

scholarly journals Regulatory T Cell–Resistant CD8+ T Cells Induced by Glucocorticoid-Induced Tumor Necrosis Factor Receptor Signaling

2008 ◽  
Vol 68 (14) ◽  
pp. 5948-5954 ◽  
Author(s):  
Hiroyoshi Nishikawa ◽  
Takuma Kato ◽  
Michiko Hirayama ◽  
Yuki Orito ◽  
Eiichi Sato ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Cd8 T Cells ◽  
Regulatory T Cell ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Receptor Signaling ◽  
Necrosis Factor

scholarly journals Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Trine B. Levring ◽  
Martin Kongsbak-Wismann ◽  
Anna K. O. Rode ◽  
Fatima A. H. Al-Jaberi ◽  
Daniel V. Lopez ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Glucose Uptake ◽  
Tumor Necrosis ◽  
Gradient Centrifugation ◽  
Tumor Necrosis Factor Receptor ◽  
Down Regulation ◽  
Interacting Protein ◽  
Human T Cells ◽  
Necrosis Factor

Abstract In addition to antigen-driven signals, T cells need co-stimulatory signals for robust activation. Several receptors, including members of the tumor necrosis factor receptor superfamily (TNFRSF), can deliver co-stimulatory signals to T cells. Thioredoxin interacting protein (TXNIP) is an important inhibitor of glucose uptake and cell proliferation, but it is unknown how TXNIP is regulated in T cells. The aim of this study was to determine expression levels and regulation of TXNIP in human T cells. We found that naïve T cells express high levels of TXNIP and that treatment of blood samples with TNF results in rapid down-regulation of TXNIP in the T cells. TNF-induced TXNIP down-regulation correlated with increased glucose uptake. Furthermore, we found that density gradient centrifugation (DGC) induced down-regulation of TXNIP. We demonstrate that DGC induced TNF production that paralleled the TXNIP down-regulation. Treatment of blood with toll-like receptor (TLR) ligands induced TNF production and TXNIP down-regulation, suggesting that damage-associated molecular patterns (DAMPs), such as endogenous TLR ligands, released during DGC play a role in DGC-induced TXNIP down-regulation. Finally, we demonstrate that TNF-induced TXNIP down-regulation is dependent on caspase activity and is caused by caspase-mediated cleavage of TXNIP.

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