Blocking the inhibitory receptor programmed cell death 1 prevents allergic immune response and anaphylaxis in mice.
J Allergy Clin Immunol
; 150(1): 178-191.e9, 2022 07.
Article
en En
| MEDLINE
| ID: mdl-35092762
ABSTRACT
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Hipersensibilidad al Cacahuete
/
Anafilaxia
Límite:
Animals
Idioma:
En
Revista:
J Allergy Clin Immunol
Año:
2022
Tipo del documento:
Article