Uveitis is an important autoimmune disease affecting an estimated 2.3 million Americans. This disease is manifested by inflammation of the retina mediated by the infiltration of T lymphocytes that recognize "S-Antigen" (S-Ag). Current therapies involve the life-long use of immunosuppressive drugs, including steroids. The ability to induce specific tolerance to S-Ag would be desirable and allow patients to be weaned off of steroid therapy. In this study, we determined that S-Ag-Ig retroviral vector was capable of preventing EAU (experimental autoimmune uveoretinitis) in Lewis rats induced by immunization with bovine S-Ag (BoS-Ag). Importantly, B-cell delivered gene therapy with S-Ag-Ig can ameliorate ongoing EAU when the treatment was initiated after rats had been immunized. Furthermore, we have successfully induced tolerance in HLA-DR3 transgenic mice with respect to the T-cell proliferative response. These results demonstrate proof of principle for future efforts to develop this approach for clinical application in patients with uveoretinitis.
- B cells
- Gene therapy