Targeted Antigen Delivery to DEC-205+ Dendritic Cells for Tolerogenic Vaccination

Article View

The Review of Diabetic Studies,2012,9,4,305-318.
Published:February 2013
Type:Review Article
Author(s) affiliations:

Cathleen Petzold1, Sonja Schallenberg1, Joel N.H. Stern2, and Karsten Kretschmer1

1Immunotolerance in Regeneration, Center for Regenerative Therapies Dresden, Dresden, Germany.

2Department of Cancer Immunology and AIDS, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA, USA.


Dendritic cells (DCs) and Foxp3-expressing CD4+ regulatory T (Treg) cells play non-redundant roles in the maintenance of peripheral tolerance to self-antigens, thereby preventing fatal autoimmunity. A common hallmark of intra- and extrathymic Treg cell lineage commitment is the induction of Foxp3 expression as a consequence of appropriate T cell receptor engagement with MHC class II:agonist ligand. It has now become increasingly clear that agonist ligand presentation by immature DCs in the steady state induces T cell tolerance by both recessive and dominant mechanisms, rather than promoting productive T helper cell responses. In this context, the ability of steady-state DCs to promote the extrathymic conversion of initially naïve CD4+Foxp3- T cells into Foxp3+ Treg cells is of particular interest as it provides novel perspectives to enhance antigen-specific Treg cell function in clinical settings of unwanted immunity, such as β-cell autoimmunity.