Characterization and functional study of five novel monoclonal antibodies against human OX40L highlight reverse signalling: enhancement of IgG production of B cells and promotion of maturation of DCs

Wang, Q.; Chen, Y.; Ge, Yan; Sun, Jing; Shi, Qin; Ju, Songwen; Jun, Dai; Yu, Guang-Di; Zhang, X.

doi:10.1111/j.1399-0039.2004.00300.x

Cited by 21 publications

(13 citation statements)

References 30 publications

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“…In the absence of inflammation, therefore, TRAF-6 degradation is slower. The binding of T-cellexpressed OX40 to OX40L drives the production of IFN-γ and TNF by both participating cells (28,29), which may override the osteoclastogenic activity of RANK-L. It is also possible that reverse signaling by OX40L may directly activate the ubiquitinproteasome system or TRAF-6 ubiquitination without the requirement for inflammatory cytokines.…”

Section: Resultsmentioning

confidence: 99%

OX40L blockade is therapeutic in arthritis, despite promoting osteoclastogenesis

Findlay

Danks²,

Madden

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Current therapies to alleviate autoimmune conditions use global strategies that affect large compartments of the immune response. These strategies mop up the excesses of disease without slowing disease progression and carry a significant risk of infection. This article describes the selective inhibition of autoaggressive T cells with the ability to regress established arthritis and reveals an unexpected role for an immune receptor–ligand pair in bone homeostasis.

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Section: Resultsmentioning

confidence: 99%

OX40L blockade is therapeutic in arthritis, despite promoting osteoclastogenesis

Findlay

Danks²,

Madden

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…An alternative explanation could be that the anti‐OX40‐L antibody delivered a positive signal to the B‐lymphocytes producing anti‐mouse immunoglobulin. Support for this comes from the observation that OX40‐signalling in vitro enhanced both the proliferation and immunoglobulin secretion of human 40,41 and murine 42 B lymphocytes stimulated by mitogen or CD40 cross‐linking in vitro . Mercuric chloride polyclonally activates B lymphocytes and may have been a cofactor in enhancing the antibody response to a foreign protein.…”

Section: Discussionmentioning

confidence: 99%

Blockade of OX40‐ligand after initial triggering of the T helper 2 response inhibits mercuric chloride‐induced autoimmunity

2006

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Summary Mercuric chloride (HgCl2)‐induced autoimmunity in Brown Norway rats is a spontaneously resolving autoimmune response driven by the activation of T helper type 2 lymphocytes (Th2 cells). Treatment with antibody to OX40‐ligand (OX40‐L) from the time of the first HgCl2 injection for 12 days had little effect. Delayed treatment commenced 8 days after the first HgCl2 injection significantly suppressed immunoglobulin E production, splenomegaly, weight loss and mortality. This makes OX40/OX40‐L signalling an attractive therapeutic target for Th2‐driven autoimmune diseases. Intravenous administration of the murine antibody to OX‐40‐L elicited a vigorous anti‐mouse immunoglobulin antibody response that was significantly enhanced compared to the response to control immunoglobulin. It is likely that this response significantly reduced the plasma half‐life of the anti‐OX40‐L antibody and this observation has clear implications for the interpretation of data from experiments where anti‐OX40‐L is used in vivo.

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“…In addition, outside-to-inside signal transmitted by CD27L or FasL leads to T-cell proliferation [80–82]. Enhancement of IgG production of B cells and promotion of maturation of DCs were shown to be reverse signalling by OX40L [83]. Outside-to-inside signals have been studied relatively well for the CD137L.…”

Section: Biological Activities Of Transmembrane Tnf-α As a Receptormentioning

confidence: 99%

Transmembrane TNF- : structure, function and interaction with anti-TNF agents

et al. 2010

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Transmembrane TNF-α, a precursor of the soluble form of TNF-α, is expressed on activated macrophages and lymphocytes as well as other cell types. After processing by TNF-α-converting enzyme (TACE), the soluble form of TNF-α is cleaved from transmembrane TNF-α and mediates its biological activities through binding to Types 1 and 2 TNF receptors (TNF-R1 and -R2) of remote tissues. Accumulating evidence suggests that not only soluble TNF-α, but also transmembrane TNF-α is involved in the inflammatory response. Transmembrane TNF-α acts as a bipolar molecule that transmits signals both as a ligand and as a receptor in a cell-to-cell contact fashion. Transmembrane TNF-α on TNF-α-producing cells binds to TNF-R1 and -R2, and transmits signals to the target cells as a ligand, whereas transmembrane TNF-α also acts as a receptor that transmits outside-to-inside (reverse) signals back to the cells after binding to its native receptors. Anti-TNF agents infliximab, adalimumab and etanercept bind to and neutralize soluble TNF-α, but exert different effects on transmembrane TNF-α-expressing cells (TNF-α-producing cells). In the clinical settings, these three anti-TNF agents are equally effective for RA, but etanercept is not effective for granulomatous diseases. Moreover, infliximab induces granulomatous infections more frequently than etanercept. Considering the important role of transmembrane TNF-α in granulomatous inflammation, reviewing the biology of transmembrane TNF-α and its interaction with anti-TNF agents will contribute to understanding the bases of differential clinical efficacy of these promising treatment modalities.

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Characterization and functional study of five novel monoclonal antibodies against human OX40L highlight reverse signalling: enhancement of IgG production of B cells and promotion of maturation of DCs

Cited by 21 publications

References 30 publications

OX40L blockade is therapeutic in arthritis, despite promoting osteoclastogenesis

OX40L blockade is therapeutic in arthritis, despite promoting osteoclastogenesis

Blockade of OX40‐ligand after initial triggering of the T helper 2 response inhibits mercuric chloride‐induced autoimmunity

Transmembrane TNF- : structure, function and interaction with anti-TNF agents

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