Preliminary studies have suggested that a new therapeutic modality may be valuable in the management of cutaneous T cell lymphoma (CTCL) and the autoimmune disease pemphigus vulgaris (PV). In this treatment, lymphapheresis samples containing 8-methoxypsoralen (8MOP) are passed through an ultraviolet A (UVA) light exposure field. The photo-activated 8MOP cross-links the lymphocyte DNA and the treated cells are reinfused into the patient. Response to this therapy has been demonstrated by clearance of skin lesions and reduction of circulating tumor cells in CTCL and loss of anti-keratinocyte antibody titers in PV. Clinical response has been accompanied by alterations in T cell subsets, following reinfusion of the treated samples. Therefore, it appears that the mechanism(s) involved relate to the host response to 8MOP-UVA treated cells. The purpose of this proposal is to investigate the mechanism(s) underlying this therapy in experimental models. It is theorized that the mechanism by which 8MOP-UVA mediates immune suppression of neoplasia and autoimmune disease involves recognition of abnormal antigens on the lymphocyte surface and induction of an anti-idiotypic cellular and humoral response to these determinants. This proposition can be directly tested in autoimmune mice since their B lymphocytes express an abnormal autoreactive idiotype which escapes immune surveillance. To investigate the mechanism(s) by which 8MOP-UVA photo-therapy effects the immune response two experimental models will be developed. In the second normal mice will be sensitized to alloantigens and the 8MOP treated splenocytes used to transfer alloreactive lymphocytes to naive recipients. The recipient mice will then be challenged with an allograft. Elucidation of the mechanism(s) by which 8MOP-UVA therapy modulates immune regulation may facilitate the development of an improved therapy for selected leukemias, autoimmune disease, and an adjunct therapy for transplantation.
