scholarly journals Functional characterization of the human tumor necrosis factor receptor p75 in a transfected rat/mouse T cell hybridoma.

1992 ◽  
Vol 176 (4) ◽  
pp. 1015-1024 ◽  
Author(s):  
P Vandenabeele ◽  
W Declercq ◽  
D Vercammen ◽  
M Van de Craen ◽  
J Grooten ◽  
...  
Keyword(s):  
T Cells ◽  
Biological Activity ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Functional Characterization ◽  
Human Tumor ◽  
Human Tumor Necrosis Factor ◽  
Necrosis Factor

We investigated the biological role of the human tumor necrosis factor p75 (hTNF-R75), making use of the species specificity of TNF responses in murine (m) T cell lines. Several TNF-mediated activities on mouse T cells, such as cytokine induction or proliferation, showed a 100-500-fold difference in specific biological activity between mTNF and hTNF. After transfection of hTNF-R75 cDNA in a rat/mouse T cell hybridoma (PC60), however, the 100-fold lower specific biological activity of hTNF was converted to the same specific biological activity as mTNF. The TNF-mediated induction of granulocyte/macrophage colony-stimulating factor was strongly synergized by the addition of interleukin 1. In the presence of the latter cytokine, ligand-competing monoclonal antibodies against hTNF-R75 (utr-1, utr-2, utr-3) were agonistic on transfected PC60 cells. This agonistic activity was further enhanced by crosslinking with sheep anti-murine immunoglobulin antibodies. These data provide direct evidence for a functional role of TNF-R75, without ligand-dependent TNF-R55 involvement, in the induction of cytokine secretion in T cells.

scholarly journals In vivoAntitumor Mechanism of Natural Human Tumor Necrosis Factor Involving a T Cell-mediated Immunological Route

1989 ◽  
Vol 80 (12) ◽  
pp. 1161-1164 ◽  
Author(s):  
Tetsuya Asami ◽  
Meroni Imai ◽  
Yasuo Tanaka ◽  
Yoshitaka Hosaka ◽  
Kazuharu Kato ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Human Tumor ◽  
Human Tumor Necrosis Factor ◽  
Necrosis Factor

scholarly journals Insertion of Foreign T Cell Epitopes in Human Tumor Necrosis Factor α with Minimal Effect on Protein Structure and Biological Activity

2004 ◽  
Vol 279 (32) ◽  
pp. 33593-33600 ◽  
Author(s):  
Finn Stausholm Nielsen ◽  
Jørgen Sauer ◽  
Johan Bäcklund ◽  
Bjørn Voldborg ◽  
Klaus Gregorius ◽  
...  
Keyword(s):  
Biological Activity ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Human Tumor ◽  
Minimal Effect ◽  
T Cell Epitopes ◽  
Human Tumor Necrosis Factor ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor.

1992 ◽  
Vol 175 (1) ◽  
pp. 91-98 ◽  
Author(s):  
T Miethke ◽  
C Wahl ◽  
K Heeg ◽  
B Echtenacher ◽  
P H Krammer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Staphylococcal Enterotoxin B ◽  
Toxic Shock ◽  
Lethal Shock ◽  
Enterotoxin B ◽  
Necrosis Factor

Because mice are more resistant than humans to the pathogenic effects of bacterial toxins, we used D-Galactosamine- (D-Gal) sensitized mice as a model system to evaluate potential toxic shock symptoms triggered by the superantigen staphylococcal enterotoxin B (SEB). We show that similar to endotoxin (lipopolysaccharide) [LPS], the exotoxin SEB causes lethal shock within 8 h in D-Gal-sensitized mice, inducing 100% and about 50% lethality with 20 and 2 micrograms SEB, respectively. The lethal shock triggered by the superantigen SEB is mediated by T cells, a conclusion based on the observation that T cell repopulation of SCID mice conferred sensitivity to SEB. Since CSA also conferred protection, the role of T cell-derived lymphokines in mediating lethal shock was evaluated. Within 30-60 min after SEB injection, serum tumor necrosis factor (TNF) levels peaked, followed immediately by interleukin-2 (IL-2). Serum-borne lymphokines were detected well in advance of signs of T cell activation, as assessed by IL-2 receptor expression of SEB-reactive V beta 8+ T cells. Passive immunization with anti-TNF-alpha/beta-neutralizing monoclonal antibody also conferred protection, indicating that it is TNF which is critical for initiating toxic shock symptoms. Taken together, this study defines basic differences between endotoxin (LPS)- and exotoxin (SEB)-mediated lethal shock, in that the former is mediated by macrophages and the latter by T cells. Yet the pathogenesis distal to the lymphokine/cytokine-producing cells appears surprisingly similar in that TNF represents a key mediator in inducing shock.

scholarly journals The TNF-α/TNFR2 Pathway: Targeting a Brake to Release the Anti-tumor Immune Response

2021 ◽  
Vol 9 ◽  
Author(s):  
Audrey Moatti ◽  
José L. Cohen
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Signaling Pathway ◽  
Immune Checkpoint ◽  
Tumor Necrosis ◽  
Tnf Α ◽  
Anti Cancer ◽  
Necrosis Factor

Newly discovered anti-cancer immunotherapies, such as immune checkpoint inhibitors and chimeric antigen receptor T cells, focus on spurring the anti-tumor effector T cell (Teff) response. Although such strategies have already demonstrated a sustained beneficial effect in certain malignancies, a substantial proportion of treated patients does not respond. CD4+FOXP3+ regulatory T cells (Tregs), a suppressive subset of T cells, can impair anti-tumor responses and reduce the efficacy of currently available immunotherapies. An alternative view that has emerged over the last decade proposes to tackle this immune brake by targeting the suppressive action of Tregs on the anti-tumoral response. It was recently demonstrated that the tumor necrosis factor alpha (TNF-α) tumor necrosis factor receptor 2 (TNFR2) is critical for the phenotypic stabilization and suppressive function of human and mouse Tregs. The broad non-specific effects of TNF-α infusion in patients initially led clinicians to abandon this signaling pathway as first-line therapy against neoplasms. Previously unrecognized, TNFR2 has emerged recently as a legitimate target for anti-cancer immune checkpoint therapy. Considering the accumulation of pre-clinical data on the role of TNFR2 and clinical reports of TNFR2+ Tregs and tumor cells in cancer patients, it is now clear that a TNFR2-centered approach could be a viable strategy, once again making the TNF-α pathway a promising anti-cancer target. Here, we review the role of the TNFR2 signaling pathway in tolerance and the equilibrium of T cell responses and its connections with oncogenesis. We analyze recent discoveries concerning the targeting of TNFR2 in cancer, as well as the advantages, limitations, and perspectives of such a strategy.

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