OX40 is a secondary co-stimulatory immune checkpoint molecule, expressed after 24 to 72 hours following activation; its ligand, OX40L, is also not expressed on resting antigen presenting cells, but is following their activation.

This review provides a broad overview of the biology of OX40, and the intracellular signals from OX40, that impact many aspects of immune function, and have promoted OX40 as one of the most prominent costimulatory molecules known to control T cells.

OX40L is the ligand for OX40 (also known as CD134 or TNFRSF4) and is stably expressed on many antigen-presenting cells such as DC2s (a subtype of dendritic cells), [1] macrophages, [2] and activated B lymphocytes.

The tumour necrosis factor receptor OX40 (CD134) is activated by its cognate ligand OX40L (CD134L, CD252) and functions as a T cell co-stimulatory molecule. OX40-OX40L interactions have been proposed as a potential therapeutic target for treating autoimmunity.

Reagents that interfere with the binding of OX40 to OX40L have been shown to inhibit T cell responses and pathogenic symptoms in a number of immune based diseases. Conversely reagents that augment OX40 signals have now shown therapeutic efficacy in models of cancer.

The optimal expression of OX40 occurs 24-48 hours after the activation of naïve T cells and requires the presence of three signals: 1) strong TCR ligation; 2) CD28 engagement; and 3) IL-2/IL-2R signaling.

Binding of OX40 to OX40L induces signal transduction pathways to activate immune response and regulate T-cell activation, proliferation, differentiation, expansion, and survival. Evidence also suggests a role of OX40 in Th1 and Th2 response [9, 10].

OX40 is a type 1 transmembrane glycoprotein, reported nearly 30 years ago as a cell surface antigen expressed on activated T cells. Since its discovery, it has been validated as a bone fide costimulatory molecule for T cells and member of the TNF receptor family.

2020年3月1日 · This review discusses the biology of OX40 and OX40L and summarizes the impact of the OX40–OX40L interaction on T cell subsets to provide a comprehensive understanding of anti-OX40 mAbs-based therapy.

2004年6月1日 · In vivo blockade of OX40 signalling specifically suppresses the function of recently activated autoantigen-specific T cells, leading to inhibition of autoimmune disease without severe ...