Extending the Horizon for Cell-Based Immunotherapy by Understanding the Mechanisms of Action of Photopheresis

Most of the current cell-based immunotherapy protocols concentrate on immune stimulatory effects against certain pathogenic insults, such as cancer. In this article, a potential cell-based immunotherapeutic strategy to induce immune tolerance by infusion of apoptotic leukocytes is presented in conjunction with a review of newly understood mechanisms of action of photopheresis and relevant information about allogeneic transfusion-related immunomodulation. The scientific rationale is discussed by examining our understanding of the role of apoptosis in self-antigen tolerance, the interaction between apoptotic bodies and antigen-presenting cells, and the subsequent induction of T regulatory cells and clonal deletion of effector T cells. Previous data on transfusion-related immunomodulation are assembled to examine a possible link between the immunosuppressive effects obtained from photopheresis and those seen post allogeneic blood transfusion. Accumulating evidence appears to support the hypothesis that photopheresis and allogeneic blood transfusion may share a mechanism of action for the induction of immunosuppression, which suggests the potential of eliciting selective immune tolerance by giving the recipient a bolus of apoptotic cells. Such immunotherapy interventions could bring significant clinical benefit to patients undergoing transplant rejection or autoimmune-related disorders and deserve further investigation as well as validation studies.