CD137 (ILA/4-1BB), expressed by primary human monocytes, induces monocyte activation and apoptosis of B lymphocytes

Kienzle, Georg; Kempis, Johannes von

doi:10.1093/intimm/12.1.73

Cited by 80 publications

(68 citation statements)

References 48 publications

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“…Reverse signaling following cross-linking of 4-1BBL in lymphocytes inhibits proliferation and induces apoptosis Ebta et al, 2001). In addition, 4-1BB also causes apoptosis of B-cells by direct cell contact (Kienzle and Kempis, 2000).…”

Section: Discussionmentioning

confidence: 99%

Serum concentrations of soluble 4-1BB and 4-1BB ligand correlated with the disease severity in rheumatoid arthritis

Jung

Choi²,

Choi³

et al. 2004

Exp Mol Med

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Abbreviations: BD, Behcet's disease; RA, rheumatoid arthritis; s4-1BB, soluble 4-1BB; s4-1BBL, soluble 4-1BB ligand; SLE, systemic lupus erythematosus A bstract R heum atoid arthritis (R A ) is a m ultifactorial autoim m une disease w hose etiopathogenesis is not w ell understood. Although soluble (s) form s of 4-1BB (s4-1BB) and 4-1BB legand (s4-1BBL) have been detected in the sera of RA patients, their significance is not know n. W e com pared the serum levels of s4-1BB and s4-1BBL in RA patients w ith those in system ic lupus erythem atosus (SLE) and Behcet's disease (BD) patients. Serum levels of s4-1BB and s4-1BBL w ere significantly higher in RA patients com pared w ith healthy controls, SLE or BD patients, and the abundance w as correlated w ith disease severity in patients w ith RA. The serum levels of s4-1BB in RA patients w ere inversely corroborated w ith 4-1BB expression levels on activated T lym phocytes. In addition, there was a correlation betw een serum levels of s4-1BB and s4-1BBL. The augm ented secretion of s4-1BB and s4-1BBL levels into the serum m ay reflect the clinical sym ptom s of RA and levels of s4-1BB and s4-1BBL in sera at the tim e of diagnosis m ay be indicative of the severity and outcom e of RA.

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Section: Discussionmentioning

confidence: 99%

Serum concentrations of soluble 4-1BB and 4-1BB ligand correlated with the disease severity in rheumatoid arthritis

Jung

Choi²,

Choi³

et al. 2004

Exp Mol Med

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“…Total RNA (2 lg) was reverse-transcribed with (dT) 16 and 1 lL of Superscript II enzyme (Invitrogen, Carlsbad, CA) in 20 lL reaction mix at 42 C for 1 h. For real-time PCR, a 20-lL reaction mix containing 1 lL template cDNA, SYBR Premix Ex Taq, ROX Reference Dye (Takara Bio, Otsu, Japan), and each primer (0.2 lM) was prepared and subjected to amplification using a fluorescence thermocycler (Applied Biosystems 7500 Real-time PCR, Foster City, CA) under the following conditions: initial denaturation at 94 C for 1 min, followed by 40 cycles of denaturation at 95 C for 15 s, annealing at 60 C for 15 s, and elongation at 72 C for 33 s. The specificity of the PCR product was verified by melting curve analysis and examination on a 3% agarose gel. The housekeeping GAPDH gene was amplified in parallel with the gene of interest.…”

Section: Real-time Sqrt-pcrmentioning

confidence: 99%

“…In addition, the intracellular signaling pathways downstream of 4-1BB and RANK are very similar [13,14]. Recent studies showed that 4-1BB is expressed on dendritic cells and monocytes as well as on T cells, and modulates the function of these cells [15,16]. Furthermore, reverse signaling through 4-1BBL on monocytes induces the secretion of inflammatory cytokines, monocyte proliferation, and endomitosis [17,18].…”

Section: Introductionmentioning

confidence: 99%

The 4–1BB ligand and 4–1BB expressed on osteoclast precursors enhance RANKL‐induced osteoclastogenesis via bi‐directional signaling

et al. 2008

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The 4-1BB is a costimulatory molecule similar to the receptor activator of NF-jB ligand (RANKL), both of which are key factors for the differentiation of osteoclasts and are expressed mainly by activated T cells. The 4-1BB shares common signaling pathways with RANK, suggesting a potential role in osteoclastogenesis. In this study, the role of 4-1BB and 4-1BB ligand (4-1BBL) in osteoclastogenesis was investigated using 4-1BB -/-and 4-1BB +/+ mice. Osteoclast precursors normally express 4-1BB and 4-1BBL after exposure to RANKL, which was confirmed by semi-quantitative RT-PCR and flow cytometry. The 4-1BB -/-mice had a slightly increased bone mass accompanied by a reduced osteoclastogenic ability of 4-1BB -/-bone marrow-derived macrophages (BMM) ex vivo. In addition, 4-1BB -/-BMM demonstrated hypophosphorylation of JNK and p38 and decreased induction of c-Fos in response to RANKL stimulation. Retroviral transduction of wild-type as well as partiallength 4-1BB, which lacks TNF receptor-associated factor 2-binding sites for signaling, restored the osteoclastogenic ability of 4-1BB -/-BMM. Furthermore, both recombinant 4-1BB and 4-1BBL enhanced RANKL-induced osteoclastogenesis by 4-1BB +/+ BMM and the induction of c-Fos and NFATc1.Together, these results indicate that 4-1BBL and 4-1BB expressed on osteoclast precursors enhance RANKL-induced osteoclastogenesis via bi-directional signaling, findings that may delineate the complex nature of the 4-1BBL and 4-1BB interaction.

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“…18 In addition to CD4 þ and CD8 þ T cells, 4-1BB was also expressed on activated natural killer (NK), 22 dendritic cells (DC) 23 as well as neutrophils 24 in mice. In humans, the expression of 4-1BB was been reported in follicular DCs, 25 monocytes, 26 hepatoma cells 18 and blood vessels from individuals with malignant tumors. 27 The soluble form of 4-1BB was also reported in the serum of patients with rheumatoid arthritis.…”

Section: Expression Of 4-1bb and 4-1bbl In Vivomentioning

confidence: 97%

Role of 4-1BB:4-1BB ligand in cancer immunotherapy

2003

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The activation of T cells plays a central role in antitumor immunity. In order to activate naïve T cells, two key signals are required. Signal one is provided through the T-cell receptor (TCR) while signal two is that of costimulation. The CD28:B7 molecules are one of the best-studied costimulatory pathways, thought to be the main mechanism through which primary T-cell stimulation occurs. However, a number of molecules have been identified which serve to amplify and diversify the T-cell response, following initial Tcell activation. These include the more recently described 4-1BB:4-1BB ligand (4-1BBL) molecules. 4-1BB:4-1BBL are a member of the TNFR:TNF ligand family, which are expressed on T cells and antigen-presenting cells (APCs), respectively. Therapies utilizing the 4-1BB:4-1BBL signaling pathway have been shown to have antitumor effects in a number of model systems. In this paper, we focus on the 4-1BB:4-1BBL costimulatory molecules. In particular, we will describe the structure and function of the 4-1BB molecule, its receptor and how 4-1BB:4-1BBL costimulation has and may be used for the immunotherapy of cancer.

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CD137 (ILA/4-1BB), expressed by primary human monocytes, induces monocyte activation and apoptosis of B lymphocytes

Cited by 80 publications

References 48 publications

Serum concentrations of soluble 4-1BB and 4-1BB ligand correlated with the disease severity in rheumatoid arthritis

Serum concentrations of soluble 4-1BB and 4-1BB ligand correlated with the disease severity in rheumatoid arthritis

The 4–1BB ligand and 4–1BB expressed on osteoclast precursors enhance RANKL‐induced osteoclastogenesis via bi‐directional signaling

Role of 4-1BB:4-1BB ligand in cancer immunotherapy

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