LOCAL-DELIVERY OF CYTOKINES BY RETROVIRALLY TRANSDUCED ANTIGEN-SPECIFIC TCR+ HYBRIDOMA CELLS IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Autoimmune diseases in humans represent an immune attack on self tissu e. Current therapies for almost all autoimmune diseases utilize potent and nonspecific immunosuppressive regimens. These therapies are compl icated by their side effects and also place the patient at increased r isk for opportunistic infections and malignancies. Our current underst anding of immune mechanisms underlying autoimmune diseases remains lim ited. Ongoing studies include identifying genes that predispose an ind ividual to developing autoimmunity, identification of autoantigens tha t trigger or perpetuate autoimmunity, and studies of immune cell inter actions that lead to immune response. Although it may be many years be fore a full understanding of autoimmunity is obtained, treatment in an imal models of autoimmune disease and some human clinical trials have begun to study alternative treatment approaches to therapy of autoimmu ne disease. Future therapies for autoimmune diseases should target the inappropriate autoimmnne response. This article will describe the use of gene therapy in the treatment of autoimmune disease. We believe th at autoimmunity can be ameliorated by delivering trans-acting immunore gulatory molecules by retrovirally transduced autoantigen specific T c ells that home to lesions of autoimmunity. Until recently, there has n ot been a practical alternative to systemic delivery of immunoregulato ry molecules, however systemic delivery suffers from toxic side effect s and dangerous global immunosuppression, In order to study immune reg ulation using retroviral transduction for local delivery of immunoregu latory products, we used myelin basic protein (MBP) reactive T cell hy bridomas in the marine model of multiple sclerosis (MS), experimental allergic encephalomyelitis (EAE), In this report, we show that MBP rea ctive T cell hybridomas transduced to express IL-4 or TNF, ameliorated or exacerbated disease, respectively, Additionally, the effects of th ese cells were dependent on T cell receptor (TCR) expression, indicati ng that the effects were due to homing of the T cells and the local de livery of cytokines, We believe that gene therapy, allowing local deli very of immunoregulatory proteins by autoantigen specific T cells, rep resents an interesting potential therapy for autoimmune disease.