**8. "Inverse vaccination "to reduce the immune response**

Traditional vaccination is strengthening the immune reaction against an antigen, usually an infectious microbe. Methods of reducing a pathological specific immune response eg in auto‐ immune diseases like T1D can be regarded as a sort of "inverse" vaccination. In allergy toler‐ ance against the allergens is created by presenting the antigen/allergen/s in gradually increasing doses. Such Immunotherapy has become quite efficacious [55] and the adverse events are rare.

It would be reasonable to try to reduce an autoimmune process in an analogue way, by ad‐ ministration of auto-antigen/s. Thus, instead of suppressing the immune system, the immune response should be modulated by presenting antigen/s in a way that the immune system shifts from a destructive process to tolerance [56].

If self-reactive T-cells directed against auto-antigens cause some cases of Type 1 diabetes a major question is why such self-reactive T-cells occur. Two mechanisms seem to be necessary for self-tolerance: Clonal deletion of self-reactive T-cells issued from the random recombina‐ tion of genes (negative selection), and generation of self-antigen-specific natural regulatory Tcells (Tregs) which can inactivate self-reactive T-cells in the periphery when they have escaped intra-thymic negative selection [57]. In T1D auto-reactivity against insulin is a common and early phenomenon. The important role of thymic insulin for development of self-tolerance has been demonstrated in transgenic mice [58], but there is still no technique to use this knowledge in clinical practice.
