Switching off immunity: the mechanism of antigen-specific immunotherapyity

The regulation of immune responses to self and foreign antigens is vitally important to limit immune pathology associated with both infections and hypersensitivity conditions. Control of autoimmune and allergic conditions can be reinforced by tolerance induction with peptide epitopes; this presentation will focus on the mechanisms involved. Peptides must mimic naturally processed epitopes. Peptide induced peripheral tolerance is characterised by the generation of anergic, IL-10 secreting CD4+ T-cells with regulatory function. CD4+ T-cells become anergic following their first encounter with peptide. The loss of proliferative capacity correlates with a cytokine switch from a pro-inflammatory to a phenotype characterised by secretion of the anti-inflammatory cytokine IL-10. IL-10 Treg cells suppress dendritic cell maturation, prevent Th cell differentiation and create a negative feedback loop for Th driven immune pathology. Tolerance induction involves upregulation of transcription factors controlling IL-10 and inhibitory receptors limiting T cell signalling. Results from clinical trials of peptide immunotherapy will be discussed.