In this study, we have identified an enzyme-substrate relationship between Trx1 and CD30, a receptor of activated lymphocytes involved in the regulation of inflammation. As lymphocytes migrate between different microenvironments, it is conceivable that Trx1 catalyzes disulfide exchange dynamically, activating or inactivating the CD30 pathway in response to the redox environment. The interaction between Trx1 and CD30 might represent a regulatory link between oxidative stress and lymphocyte function. Understanding of this relationship in vivo awaits the generation of suitable experimental tools.