Blocking the inhibitory receptor programmed cell death 1 prevents allergic immune response and anaphylaxis in mice

Background: Food allergy and acute anaphylaxis can be life-threatening. While T follicular helper (Tfh) cells play a pivotal role in the allergic immune responses, the immunologic mechanisms that regulate the production of antibodies (Abs) that mediate anaphylaxis are not fully understood. Objective: The aim of this study was to investigate the role of the inhibitory receptor programmed cell death protein 1 (PD-1), which is highly expressed on Tfh cells, in allergic immune responses using an animal model of peanut allergy and anaphylaxis. Methods: Naive wild-type mice were exposed to peanut flour intranasally and then challenged with peanut extract to induce systemic anaphylaxis. The roles of PD-1 were examined by blocking Abs and using gene-deficient animals. A hapten model and passive cutaneous anaphylaxis were used to characterize allergen-specific Abs. Results: Treatment with anti–PD-1 enhanced development of Tfh cells and germinal center B cells in mice exposed to peanut flour. Nonetheless, anti–PD-1 or its ligand fully protected mice from developing anaphylaxis. Anti–PD-1 treatment or genetic deficiency of PD-1 in CD4⁺ T cells inhibited production of peanut-specific IgE and increased the levels of IgG. The passive cutaneous anaphylaxis showed that peanut-specific Abs generated in anti–PD-1–treated animals prevented, rather than provoked, anaphylaxis when transferred to naive animals. Anti–PD-1 promoted production of Abs with low affinity for an antigen in the hapten model. Conclusion: Blockade of the pathway between PD-1 and its ligand is protective against allergic immune responses. The direct interaction between Tfh cells and B cells may play a pivotal role in controlling Ab quality and clinical manifestation of allergic diseases.