scholarly journals Activated T Cells Induce Macrophages To Produce NO and Control Leishmania major in the Absence of Tumor Necrosis Factor Receptor p55

2000 ◽  
Vol 68 (3) ◽  
pp. 1428-1434 ◽  
Author(s):  
Michelle Nashleanas ◽  
Phillip Scott
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Leishmania Major ◽  
Tumor Necrosis Factor Receptor ◽  
No Production ◽  
Activated T Cells ◽  
Necrosis Factor

ABSTRACT The ability to activate macrophages in vitro for nitric oxide production and killing of Leishmania major parasites is dependent on tumor necrosis factor, although L. major-infected mice lacking the TNF receptor p55 (TNFRp55−/− mice) or both the TNFRp55 and TNFRp75 (TNFRp55p75−/− mice) are able to produce NO in vivo and eliminate the parasites. Here we report that activated T cells cocultured with macrophages results in TNFR-independent activation sufficient to control parasites and that both CD40/CD40L and LFA-1 contribute to T-cell-mediated macrophage activation. Thus, anti-CD3-stimulated T cells activated TNFR-deficient macrophages, while T cells from CD40L−/− mice were partially defective in triggering NO production by TNFRp55p75−/− macrophages. Moreover, in the presence of gamma interferon, anti-CD40 monoclonal antibody (MAb) activated TNFR-deficient macrophages. Finally, MAb blockade of LFA-1 completely inhibited macrophage NO production. Our data indicate that T cells can activate macrophages in the absence of TNF, thus providing a mechanism for how TNFR-deficient mice can control intracellular pathogens.

Chlamydia trachomatis-infected macrophages induce apoptosis of activated T cells by secretion of tumor necrosis factor-? in vitro

2004 ◽  
Vol 193 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Michael C. Jendro ◽  
Frederik Fingerle ◽  
Tobias Deutsch ◽  
Andrea Liese ◽  
Lars K�hler ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Chlamydia Trachomatis ◽  
Tumor Necrosis ◽  
Activated T Cells ◽  
Necrosis Factor

Regulatory T Cells Expressing Tumor Necrosis Factor Receptor Type 2 Play a Major Role in CD4+ T-Cell Impairment During Sepsis

2020 ◽  
Vol 222 (7) ◽  
pp. 1222-1234 ◽  
Author(s):  
Benjamin J Gaborit ◽  
Antoine Roquilly ◽  
Cédric Louvet ◽  
Abderrahmane Sadek ◽  
Benoit Tessoulin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Regulatory T Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Cd4 T Cell ◽  
Treg Subset ◽  
Necrosis Factor

Abstract Sepsis causes inflammation-induced immunosuppression with lymphopenia and alterations of CD4+ T-cell functions that renders the host prone to secondary infections. Whether and how regulatory T cells (Treg) are involved in this postseptic immunosuppression is unknown. We observed in vivo that early activation of Treg during Staphylococcus aureus sepsis induces CD4+ T-cell impairment and increases susceptibility to secondary pneumonia. The tumor necrosis factor receptor 2 positive (TNFR2pos) Treg subset endorsed the majority of effector immunosuppressive functions, and TNRF2 was particularly associated with activation of genes involved in cell cycle and replication in Treg, probably explaining their maintenance. Blocking or deleting TNFR2 during sepsis decreased the susceptibility to secondary infection. In humans, our data paralleled those in mice; the expression of CTLA-4 was dramatically increased in TNFR2pos Treg after culture in vitro with S. aureus. Our findings describe in vivo mechanisms underlying sepsis-induced immunosuppression and identify TNFR2pos Treg as targets for therapeutic intervention.

scholarly journals N-acetyl-L-cysteine Exhibits Antitumoral Activity by Increasing Tumor Necrosis Factor α-Dependent T-Cell Cytotoxicity

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 1124-1132
Author(s):  
Yves Delneste ◽  
Pascale Jeannin ◽  
Laurent Potier ◽  
Pedro Romero ◽  
Jean-Yves Bonnefoy
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Antitumoral Activity ◽  
Lymphoma Cells ◽  
Factor Α ◽  
Necrosis Factor

Because of its anticarcinogenic and antimutagenic properties, N-acetyl-L-cysteine (NAC) has been proposed for cancer treatment. Here we present a mechanism of action for NAC in cancer. Our data show that NAC (1) induces an early and sustained increase of membrane tumor necrosis factor α (TNFα) expression on human stimulated-peripheral blood (PB) T cells and (2) increases membrane TNF-RI and TNF-RII on tumoral cell lines and on T cells after stimulation. These effects result from an early inhibition of both TNFα and TNF-R shedding, as well as a later increase of the respective mRNA expression. Consequently, NAC confers cytotoxic properties to human PB T cells through a membrane TNFα-dependent pathway. In vivo, NAC given orally inhibits tumor appearance in more than a third (18 out of 50) B6D2F1 mice injected with L1210 lymphoma cells. Spleen cells from protected mice killed L1210 lymphoma cells in vitro in a membrane TNFα-dependent manner. Furthemore these mice were resistant to a second inoculation of L1210 cells without further treatment with NAC. Thus, NAC exhibits a potent antitumoral activity by modulating TNFα and TNF-R processing without showing any in vitro and in vivo toxicity.

scholarly journals The Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Gene Modulates the Response to Candida albicans Infection

2005 ◽  
Vol 73 (11) ◽  
pp. 7502-7508 ◽  
Author(s):  
Massimiliano Agostini ◽  
Elio Cenci ◽  
Eva Pericolini ◽  
Giuseppe Nocentini ◽  
Giovanni Bistoni ◽  
...  
Keyword(s):  
T Cells ◽  
Candida Albicans ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Lower Amount ◽  
Tnf Receptor ◽  
Related Gene ◽  
Necrosis Factor

ABSTRACT The glucocorticoid-induced tumor necrosis factor (TNF) receptor-related gene (GITR; TNFRSF18) modulates immune response activating coaccessory signals in T cells and is expressed at high levels in CD4+CD25+ cells. Its ligand (GITRL) is expressed in antigen-presenting cells, where it is capable of promoting signaling. We investigated the role of GITR/GITRL interaction during disseminated candidiasis in GITR knockout (GITR−/−) mice. GITR−/− mice survived longer and had a significantly decreased yeast load in kidneys and brain compared to GITR+/+ mice. Since protective immunity to the fungus is mediated by antigen-specific T helper (Th) 1 cells, we studied in vitro cytokine production following infection. CD4+ T cells of GITR−/− mice demonstrated a more efficient Th1 polarization as suggested by a two- to threefold decreased production of interleukin- (IL-)4 and IL-10 and a four- to fivefold increased production of gamma interferon compared to GITR+/+ mice. This effect was not due to differences in lymphocyte and dendritic cell (DC) subpopulations in infected mice as demonstrated by flow cytometric studies. To verify whether DC activity was differently modulated, DCs were cocultured with CD4+ T cells in the presence of heat-inactivated Candida albicans. DCs, cocultured with GITR+/+ CD4+CD25+ cells produced a lower amount of IL-12 than DCs cocultured with GITR−/− CD4+CD25+ T cells. These results suggest that GITR regulates susceptibility to systemic candidiasis by negatively modulating IL-12 production and promoting polarization of CD4+ T cells towards Th2 by analogy with OX40, another TNF receptor superfamily member.

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

2002 ◽  
Vol 196 (1) ◽  
pp. 15-26 ◽  
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.

scholarly journals N-acetyl-L-cysteine Exhibits Antitumoral Activity by Increasing Tumor Necrosis Factor α-Dependent T-Cell Cytotoxicity

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 1124-1132 ◽  
Author(s):  
Yves Delneste ◽  
Pascale Jeannin ◽  
Laurent Potier ◽  
Pedro Romero ◽  
Jean-Yves Bonnefoy
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Antitumoral Activity ◽  
Lymphoma Cells ◽  
Factor Α ◽  
Necrosis Factor

Abstract Because of its anticarcinogenic and antimutagenic properties, N-acetyl-L-cysteine (NAC) has been proposed for cancer treatment. Here we present a mechanism of action for NAC in cancer. Our data show that NAC (1) induces an early and sustained increase of membrane tumor necrosis factor α (TNFα) expression on human stimulated-peripheral blood (PB) T cells and (2) increases membrane TNF-RI and TNF-RII on tumoral cell lines and on T cells after stimulation. These effects result from an early inhibition of both TNFα and TNF-R shedding, as well as a later increase of the respective mRNA expression. Consequently, NAC confers cytotoxic properties to human PB T cells through a membrane TNFα-dependent pathway. In vivo, NAC given orally inhibits tumor appearance in more than a third (18 out of 50) B6D2F1 mice injected with L1210 lymphoma cells. Spleen cells from protected mice killed L1210 lymphoma cells in vitro in a membrane TNFα-dependent manner. Furthemore these mice were resistant to a second inoculation of L1210 cells without further treatment with NAC. Thus, NAC exhibits a potent antitumoral activity by modulating TNFα and TNF-R processing without showing any in vitro and in vivo toxicity.

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