OX40 has no effect on the proliferative abilities of CD4+ cells for the first three days, however after this time proliferation begins to slow and cells die at a greater rate, due to an inability to maintain a high level of PKB activity and expression of Bcl-2, Bcl-XL and survivin.

OX40L binds to OX40 receptors on T-cells, preventing them from dying and subsequently increasing cytokine production.

TRAF2 is required for survival via NF-κB and memory cell generation whereas TRAF5 seems to have a more negative or modulatory role, as knockouts have higher levels of cytokines and are more susceptible to Th2-mediated inflammation.

OX40 has been implicated in the pathologic cytokine storm associated with certain viral infections, including the H5N1 bird flu.

[citation needed] An anti-OX40 antibody GSK3174998 has started clinical trials as a cancer treatment.