T-CELL VACCINATION IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS - A MATHEMATICAL-MODEL

T cell vaccination (TCV) is a method to induce resistance to autoimmun e diseases by priming the immune system with autoreactive T cells. Thi s priming evokes an anti-idiotypic regulatory T cell response to the r eceptors on the autoreactive T cells. Hence resistance is induced. To prevent the inoculated autoreactive cells from inducing autoimmunity, cells are given in a subpathogenic dose or in an attenuated form. We d eveloped a mathematical model to study how the interactions between au toreactive T cells, self epitopes, and regulatory cells can explain TC V, The model is based on detailed data on experimental autoimmune ence phalomyelitis, but can be generalized to other autoimmune diseases. We show that all of the phenomena collectively described as TCV occur qu ite naturally in systems where autoreactive T cells can be controlled by anti-idiotypic regulatory T cells. The essential assumption that we make is that TCV generally involves self epitopes for which T cell to lerance is incomplete. The model predicts a qualitative difference bet ween the two vaccination methods: vaccination with normal autoreactive cells should give rise to a steady state of long lasting protection, whereas vaccination with attenuated cells should only confer transient resistance. Moreover, the model shows how autoimmune relapses can occ ur naturally without the involvement of T cells arising due to determi nant spreading.