OX40 Signaling Pathway

OX40 is a T cell activator that is believed to promote the survival (and perhaps prolong the immune response of) CD4+ T cells at sites of inflammation. The co-stimulatory molecule OX40 Ligand (OX40L), a member of the TNF super family, is a 32 kDa protein which has a 183 aa residue glycosylated polypeptide that consists of a cytoplasmic domain, a transmembrane segment, and an extracellular region. OX40 has been shown to be important in T cell priming and cytokine production. It has a limited expression and is not constitutively present on naive T cells; its expression peaks 3-4 days after the initial activating signal and is rapidly and highly re-expressed on effector T cells. Currently, only activated CD4+, CD8+ T cells, B cells, and vascular endothelial cells have been reported to express this factor.OX40 binds OX40L and associates with adaptors TRAF2, TRAF3 and TRAF5. This results in the activation downstream of NF-κB. OX40 is also likely to activate JNK by virtue of its ability to bind TRAF2. NF-κB and JNK lead to the up-regulation of IL-2 production thereby enhancing effector and memory-effector T cell function by increasing the life span of effector T cells. OX40 can also positively regulate the anti-apoptotic molecules Bcl-XL and BCL2 thus increasing cell survival. OX40/OX40L interaction might be a vital link in our understanding of T cell mediated organ-specific autoimmunity.