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

Abstract

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. 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. 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. Ahapten model and passive cutaneous anaphylaxis were used to characterize allergen-specific Abs. 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. 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.