Advancement of antigen-specific immunotherapy: knowledge transfer between allergy and autoimmunity

Abstract

Targeted restoration of immunological tolerance to self-antigens or innocuous environmental allergens represents the ultimate aim of treatment options in autoimmune and allergic disease. Antigen-specific immunotherapy (ASI) is the only intervention that has proven disease-modifying efficacy as evidenced by induction of long-term remission in a number of allergic conditions. Mounting evidence is now indicating that specific targeting of pathogenic T cells in autoinflammatory and autoimmune settings enables effective restoration of immune homeostasis between effector and regulatory cells and alters the immunological course of disease. Here, we discuss the key lessons learned during the development of antigen-specific immunotherapies and how these can be applied to inform future interventions. Armed with this knowledge and current high-throughput technology to track immune cell phenotype and function, it may no longer be a matter of 'if' but 'when' this ultimate aim of targeted tolerance restoration is realised.

Keywords: allergy; autoimmunity; immune tolerance; immunoregulation; immunotherapy.

Figure 1

Proposed mechanism of action of bystander suppression. Antigen-specific immunotherapies prevent the generation and activation of CD4⁺ Teff and instead divert Tconv CD4⁺ cells towards anergy and also promote the expansion of antigen-specific Tr1-like cells and/or Treg. Both tolerised Tr1-like and Treg can exert cell-contact mediated and cytokine mediated suppression (dashed lines) on APC and non-antigen-specific T cells to ultimately prevent T cell activation in a non-antigen-specific manner.

Figure 2

Summarised mechanisms of action of ASI/AIT and associated risks. Antigen-specific immunotherapies have varying mechanisms of action and potential risks depending on whether they utilise (A) intact allergen, (B) intact autoantigen, or (C) peptides representing T cell epitopes of either allergen or autoantigen. Promotion of activity denoted by black arrows, inhibition of activity denoted by black dashed lines and mitigation of risks denoted by red crosses.