Regarding the roles of CD137 in disease pathogenesis, our findings strongly suggest that the abnormal membrane‐bound expression of CD137 may play a positive regulatory role in the process of ischemic injury via delivery of costimulatory signals for activation of CD4+ T cells; furthermore, enhanced plasma levels of sCD137 could stimulate a positive feedback effect that further promotes brain ischemia‐related inflammatory responses by reverse signaling. This evidence concerns the gene CD4 and brain ischemia.