T cell vaccination in experimental autoimmune encephalomyelitis: a mathematical model.
T cell vaccination (TCV) is a method to induce resistance to autoimmune diseases by priming the immune system with autoreactive T cells. This priming evokes an anti-idiotypic regulatory T cell response to the receptors 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 developed a mathematical model to study how the interactions between autoreactive T cells, self epitopes, and regulatory cells can explain TCV. The model is based on detailed data on experimental autoimmune encephalomyelitis, but can be generalized to other autoimmune diseases. We show that all of the phenomena collectively described as TCV occur quite 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 tolerance is incomplete. The model predicts a qualitative difference between 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 occur naturally without the involvement of T cells arising due to determinant spreading.
Theoretical Biology, Utrecht University, The Netherlands. jbo@binf.bio.uu.nl
J A
JA
Borghans
R J
RJ
De Boer
E
E
Sercarz
V
V
Kumar
D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D005246:Feedback; D007108:Immune Tolerance; D016219:Immunotherapy, Adoptive / Q000379:methods*; D017710:Lymphocyte Transfusion; D008432:Mathematical Computing; D051379:Mice; D008962:Models, Theoretical; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*
D001324:Autoantigens