T cell-derived tumor necrosis factor induces cytotoxicity by activating RIPK1-dependent target cell death

CD30 is a member of the tumor necrosis factor superfamily and a surface marker for Hodgkin's disease. Normal activated T cells and several virally transformed T or B cell lines also show CD30 expression. The interaction of CD30 with its ligand induces cell death or proliferation, depending on the cell type. In this report we characterize the signals mediated by the intracellular domain of CD30 and show that, in combination with signal(s) transduced by the T cell receptor, the multimerization of CD30 cytoplasmic domain induces Fas(CD95)-independent cell death in T cell hybridomas. Deletion analysis shows that the COOH-terminal 66 amino acids of CD30 are required to induce cell death. Using the yeast two-hybrid system, we have identified that the same region of CD30 interacts with tumor necrosis factor receptor-associated factor (TRAF)1 and TRAF2. These results indicate that TRAF1 and/or TRAF2 play an important role in cell death in addition to their previously identified roles in cell proliferation.

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Tumor-Induced Oxidative Stress Perturbs Nuclear Factor-κB Activity-Augmenting Tumor Necrosis Factor-α–Mediated T-Cell Death: Protection by Curcumin

Cancer Research ◽

10.1158/0008-5472.can-06-2583 ◽

2007 ◽

Vol 67 (1) ◽

pp. 362-370 ◽

Cited By ~ 60

Author(s):

Sankar Bhattacharyya ◽

Debaprasad Mandal ◽

Gouri Sankar Sen ◽

Suman Pal ◽

Shuvomoy Banerjee ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

T Cell ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Factor Α ◽

Necrosis Factor

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NFκB Controls the Balance between Fas and Tumor Necrosis Factor Cell Death Pathways during T Cell Receptor-induced Apoptosis Via the Expression of Its Target Gene A20

Journal of Biological Chemistry ◽

10.1074/jbc.m304000200 ◽

2003 ◽

Vol 278 (35) ◽

pp. 32825-32833 ◽

Cited By ~ 29

Author(s):

Michal Malewicz ◽

Nicolas Zeller ◽

Z. Buket Yilmaz ◽

Falk Weih

Keyword(s):

Cell Death ◽

T Cell ◽

Tumor Necrosis Factor ◽

T Cell Receptor ◽

Tumor Necrosis ◽

Target Gene ◽

Cell Receptor ◽

Cell Death Pathways ◽

Induced Apoptosis ◽

Necrosis Factor

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The Nef-Mediated AIDS-Like Disease of CD4C/Human Immunodeficiency Virus Transgenic Mice Is Associated with Increased Fas/FasL Expression on T Cells and T-Cell Death but Is Not Prevented in Fas-, FasL-, Tumor Necrosis Factor Receptor 1-, or Interleukin-1β-Converting Enzyme-Deficient or Bcl2-Expressing Transgenic Mice

Journal of Virology ◽

10.1128/jvi.79.10.6377-6391.2005 ◽

2005 ◽

Vol 79 (10) ◽

pp. 6377-6391 ◽

Cited By ~ 24

Author(s):

Elena Priceputu ◽

Isabelle Rodrigue ◽

Pavel Chrobak ◽

Johanne Poudrier ◽

Tak W. Mak ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Cell Death ◽

T Cell ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Receptor ◽

Converting Enzyme ◽

Immunodeficiency Virus ◽

Necrosis Factor

ABSTRACT CD4+- and CD8+-T-cell death is a frequent immunological dysfunction associated with the development of human AIDS. We studied a murine model of AIDS, the CD4C/HIV transgenic (Tg) mouse model, to assess the importance of the apoptotic pathway in human immunodeficiency virus type 1 (HIV-1) pathogenesis. In these Tg mice, Nef is the major determinant of the disease and is expressed in immature and mature CD4+ T cells and in cells of the macrophage/myeloid lineage. We report here a novel AIDS-like phenotype: enhanced death, most likely by apoptosis (as assessed by 7-aminoactinomycin D and annexin V/propidium iodide staining), of Tg thymic and peripheral CD4+ and CD8+ T cells. The Tg CD4+ and CD8+ T cells were also more susceptible to cell death after activation in vitro in mixed lymph node (LN) cultures. However, activation-induced cell death was not higher in Tg than in non-Tg-purified CD4+ T cells. In addition, expression of Fas and FasL, assessed by flow cytometry, was increased in CD4+ and CD8+ T cells from Tg mice compared to that of non-Tg littermates. Despite the enhanced expression of Fas and FasL on Tg CD4+ and CD8+ T cells, Fas (lpr/lpr) and FasL (gld/gld) mutant CD4C/HIV Tg mice developed an AIDS-like disease indistinguishable from lpr/+ and gld/+ CD4C/HIV Tg mice, including loss of CD4+ T cells. Similarly, CD4C/HIV Tg mice homozygous for mutations of two other genes implicated in cell death (interleukin-1β-converting enzyme [ICE], tumor necrosis factor receptor 1 [TNFR-1]) developed similar AIDS-like disease as their respective heterozygous controls. Moreover, the double-Tg mice from a cross between the Bcl2/Wehi25 and CD4C/HIV Tg mice showed no major protection against disease. These results represent genetic evidence for the dispensable role of Fas, FasL, ICE, and TNFR-1 on the development of both T-cell loss and organ disease of these Tg mice. They also provide compelling evidence on the lack of protection by Bcl2 against Tg CD4+-T-cell death. In view of the high resemblance between numerous phenotypes observed in the CD4C/HIV Tg mice and in human AIDS, our findings are likely to be relevant for the human disease.

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The Death Domain Kinase RIP Protects Thymocytes from Tumor Necrosis Factor Receptor Type 2–induced Cell Death

Journal of Experimental Medicine ◽

10.1084/jem.20011470 ◽

2002 ◽

Vol 196 (1) ◽

pp. 15-26 ◽

Cited By ~ 45

Author(s):

Nicole Cusson ◽

Sarah Oikemus ◽

Elizabeth D. Kilpatrick ◽

Leslie Cunningham ◽

Michelle Kelliher

Keyword(s):

T Cells ◽

Cell Death ◽

T Cell ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Receptor ◽

Receptor Activation ◽

Death Domain ◽

Necrosis Factor

Fas and the tumor necrosis factor receptor (TNFR)1 regulate the programmed cell death of lymphocytes. The death domain kinase, receptor interacting protein (rip), is recruited to the TNFR1 upon receptor activation. In vitro, rip−/− fibroblasts are sensitive to TNF-induced cell death due to an impaired nuclear factor κB response. Because rip−/− mice die at birth, we were unable to examine the effects of a targeted rip mutation on lymphocyte survival. To address the contribution of RIP to immune homeostasis, we examined lethally irradiated mice reconstituted with rip−/− hematopoietic precursors. We observed a decrease in rip−/− thymocytes and T cells in both wild-type C57BL/6 and recombination activating gene 1−/− irradiated hosts. In contrast, the B cell and myeloid lineages are unaffected by the absence of rip. Thus, the death domain kinase rip is required for T cell development. Unlike Fas-associated death domain, rip does not regulate T cell proliferation, as rip−/− T cells respond to polyclonal activators. However, rip-deficient mice contain few viable CD4+ and CD8+ thymocytes, and rip−/− thymocytes are sensitive to TNF-induced cell death. Surprisingly, the rip-associated thymocyte apoptosis was not rescued by the absence of TNFR1, but appears to be rescued by an absence of TNFR2. Taken together, this study implicates RIP and TNFR2 in thymocyte survival.

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ALLOANTIGEN-DRIVEN T CELL DEATH MEDIATED BY FAS LIGAND AND TUMOR NECROSIS FACTOR-?? IS NOT ESSENTIAL FOR THE INDUCTION OF ALLOGRAFT ACCEPTANCE1

Transplantation Journal ◽

10.1097/00007890-200006150-00037 ◽

2000 ◽

Vol 69 (11) ◽

pp. 2428-2432 ◽

Cited By ~ 16

Author(s):

Maylene E. Wagener ◽

Bogumila T. Konieczny ◽

Zhenhua Dai ◽

Guido H. Ring ◽

Fadi G. Lakkis

Keyword(s):

Cell Death ◽

T Cell ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Fas Ligand ◽

Necrosis Factor

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Les futures générations d’anticorps modulateurs des points de contrôle de la réponse immunitaire

médecine/sciences ◽

10.1051/medsci/2019193 ◽

2019 ◽

Vol 35 (12) ◽

pp. 966-974

Author(s):

Nathalie Bonnefoy ◽

Daniel Olive ◽

Bernard Vanhove

Keyword(s):

Cell Death ◽

T Cell ◽

Tumor Necrosis Factor ◽

Programmed Cell Death ◽

T Cell Activation ◽

Tumor Necrosis ◽

Cell Activation ◽

Tumor Necrosis Factor Receptor ◽

Système Immunitaire ◽

Necrosis Factor

Les points de contrôle du système immunitaire sont des systèmes moléculaires qui complètent les processus déclenchés par la reconnaissance antigénique en contrôlant l’inhibition ou l’activation des lymphocytes et des cellules myéloïdes, notamment celle des lymphocytes T régulateurs (Treg), permettant ainsi de combiner réponses immunes et maintien de la tolérance au soi. En cancérologie, l’inhibition de points de contrôle inhibiteurs vise à amplifier les réponses immunitaires existantes dirigées contre les tumeurs. Parmi ces points de contrôle inhibiteurs, dont des antagonistes sont en utilisation clinique, se trouvent CTLA-4 (cytolytic T-lymphocyte-associated antigen 4 ou CD152), PD-1 (programmed cell death 1, ou CD279), PD-L1 (programmed cell death-ligand 1, ou CD274), LAG-3 (Lymphocyte-activation gene 3, ou CD223), TIM3 (T-cell immunoglobulin and mucin-domain containing-3), TIGIT (T cell immunoreceptor with Ig and ITIM domains), VISTA (V-domain Ig suppressor of T cell activation), ou B7/H3 (ou CD276). La stimulation de points de contrôle activateurs tels que les molécules de co-activation CD28, CD137 (aussi appelé 4-1BB), OX40 [aussi appelé tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], GITR (Glucocorticoid-induced tumor necrosis factor receptor family-related protein) ou CD40, est également testée en cancérologie, le plus souvent en combinaison avec un antagoniste de point de contrôle inhibiteur. Dans les maladies auto-immunes et inflammatoires, des antagonistes de points de contrôle activateurs (CD28, CD40) et des agonistes de points de contrôle inhibiteurs (LAG-3) sont également à l’essai. Dans cette revue, nous mettons l’accent sur certains modulateurs de points de contrôle pour lesquels le mécanisme d’action a été particulièrement étudié. Cette description ne pouvant être exhaustive, nous avons regroupé dans le Tableau I l’ensemble des anticorps monoclonaux (AcM) ou protéines recombinantes en usage clinique à notre connaissance, modulant l’action d’un point de contrôle du système immunitaire.

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