| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3391535 | Seminars in Immunology | 2011 | 8 Pages |
Fopx3+ Treg safeguard against autoimmune diseases and immune pathology. The extrathymic conversion of naïve T cells into Foxp3+ regulatory T cells can be achieved in vivo by the delivery of strong-agonist ligands under subimmunogenic conditions. Tolerogenic vaccination with strong-agonist mimetopes of self-antigen to promote self-antigen specific tolerance may represent the most specific and safest means of preventing autoimmunity. This review discusses the requirements for induction of dominant tolerance exerted by Foxp3+ Tregs in autoimmunity with special emphasis on their impact to interfere with T1D. The future goals are the understanding of self-non-self discrimination at the cellular and molecular level, which should then enable investigators to develop clinical vaccination protocols that specifically interfere with unwanted immune responses.
• Subimmunogenic doses of strong-agonistic TCR ligands efficiently induce Foxp3+ Treg. • Autoantigens are recognized by autoreactive T cell receptors as weak agonists. • Weakly-agonistic autoantigens fail to efficiently induce extrathymic Tregs. • Subimmunogenic doses of strongly-agonistic variants of insulin prevent T1D in mice.
