Teaching Tolerance With a Probiotic Antigen Delivery System

Mechanisms for induction of oral tolerance. Oral administration of antigen leads to either deletion/anergy of antigen-specific T-cell clones (high dose) or induction of TGF-β-secreting regulatory T cells (Th3) (low dose). L lactis engineered to produce OVA (LL-OVA) may deliver antigen to dendritic cells: (1) via direct sampling in the intestinal lumen; or (2) through contact with DCs following penetration to the lamina propria. Oral administration of LL-OVA results in the appearance of CD4+CD25-Foxp3+CTLA-4+ regulatory T cells that may control local and systemic antigen-specific immune responses in a TGF-β-dependent manner.