It has become increasingly more evident that a considerable refinement of currently used reagents and conditions will be needed before an effective gene therapy strategy can be used in the treatment of human autoimmune diseases. Such refinements will focus on optimizing three basic requirements for effective gene therapy, viz.: (1) targeted delivery of the therapeutic gene and/or its gene product in a reliable, efficient manner; (2) long-term expression of the therapeutic gene; and (3) regulated expression of the therapeutic gene so that it is activated only when needed. Using an experimental autoimmune encephalomyelitis mouse model, we have examined the potential for using the T cell as a gene therapy vector for targeted, long-term, regulated delivery of therapeutic transgene factors to the autoimmune inflammatory milieu. Our data indicate that the autoreactive T cell may serve as a useful endogenous vector for antigen-inducible, site-specific delivery of a variety of therapeutic transgene factors capable of mediating both inhibition of autoimmune inflammation and regeneration and/or protection of damaged tissue.