Treg vaccination with a strong-agonistic insulin mimetope.

Foxp3(+) regulatory T (Treg) cells serve as a vital mechanism of negative regulation to maintain immunological self-tolerance thereby suppressing immune-mediated inflammation. The identification of the transcription factor Foxp3 as the specification factor for the Treg cell lineage facilitated our understanding in the biology of Treg generation and function. In the past, we carefully studied the extrathymic conversion of naive CD4(+) T cells into Foxp3(+) expressing Treg cells and found that this process is most efficient upon subimmunogenic supply of strong-agonistic T cell receptor (TCR) ligands avoiding activation of antigen-presenting and T cells. In contrast, weak-agonistic antigens fail to efficiently induce stable Foxp3(+) Treg cells irrespective of the applied dose. Here, we discuss the specific requirements for the establishment of Treg vaccination protocols to interfere with autoimmunity such as Type 1 diabetes.