Vaccination or tolerance to prevent diabetes.

Experiments with transgenic mice expressing the glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV) under the control of the rat insulin promoter (RIP) have demonstrated that potentially self-reactive T cells that normally ignore self peptides may nevertheless be induced by self peptides or "cross-reactive" foreign (e.g. viral) peptides that arise in the host in an immunogenic form; once activated these potentially self-reactive T cells may cause autoaggressive diseases (e.g. diabetes). The possibility of vaccinating against such T cell-mediated immunopathological diseases was evaluated in the RIP-GP transgenic mouse line Bln. Any attempt to vaccinate with the self antigen itself (e.g. recombinant vaccinia virus expressing LCMV-GP) failed to protect mice from disease. However, immunization with a recombinant vaccinia virus expressing LCMV-nucleoprotein (vacc-NP) as a non-GP LCMV vaccine was able to modulate the immune response and prevented autoaggressive disease in a MHC-dependent fashion. In contrast, tolerance induction neonatally or, more generally applicable, by lethal irradiation and reconstitution with neo-self antigen-expressing bone marrow cells always resulted in prevention of virally induced diabetes in this model situation.