Clinical and mechanistic aspects of photopheresis

Photopheresis is an extracorporeal form of photochemotherapy with 8-methoxypsoralen (8-MOP) and ultraviolet A (UVA) radiation. Photopheresis is used for the management of T-cell-mediated diseases, and such treatment leads to the induction of antigen-specific immune suppression directed to the pathogenic clone of T cells. Photopheresis is used to treat a wide variety of diseases--such as cutaneous T-cell lymphoma, systemic sclerosis; rheumatoid arthritis, lupus erythematosus--and is also successfully applied in the suppression of graft rejection. In addition to the clinical achievements, attention will be paid to results from animal studies. An important outcome of these studies is that photopheresis can be used to treat airway hyperreactivity. Furthermore, it was shown that the therapeutic strategy can be changed drastically: the presence of plasma during irradiation should be avoided and the amount of blood that must be treated to obtain the desired antigen-specific immunosuppression can be greatly decreased. Also, results from cellular experiments are discussed. An example of this is the increase in the major histocompatibility complex expression on the surface of cells found after treatment. The mechanism that underlies photopheresis has not yet been elucidated, but progress has been made. The following related points will be reviewed: models for investigation; and mechanistic aspects, with the emphasis on cellular biomacromolecules and on photosensitizers (drugs) other than 8-MOP.