Experimental Aspects of T Cell Vaccination

In the last 10 years, our laboratory has investigated the role of T cells in the induction and therapy of experimental autoimmune diseases. In several animal model T cell lines and clones that were expanded in vitro by repeated culture with the autoantigen were found to be pathogenic. Inoculation of pathogenic T cells after attenuation resulted in protection of the animals against a future attempt to induce the disease: this form of therapy was termed T cell vaccination (TCV). Several forms of TCV were developed, including the administration of T cell lines attenuated by irradiation or mitomycin C, membrane modified cells and sub-pathogenic doses of unmodified T cells. The vaccinating effect was found to be mediated by T cells. Vaccinated animals had both CD4 T cells that responded to the vaccine and CD8 T cells that suppressed its response to the autoantigen. The major obstacle to the clinical application of TCV in human autoimmune diseases is the fact that the nature of autoantigens initiating and perpetuating the disease are not known.