Elevated memory T-cell conversion in a preclinical mouse model of hemophilia A.
Activation threshold
Factor VIII
Hemophilia A
Memory T cells
Journal
European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201
Informations de publication
Date de publication:
14 Jun 2024
14 Jun 2024
Historique:
revised:
27
05
2024
received:
06
10
2023
accepted:
31
05
2024
medline:
14
6
2024
pubmed:
14
6
2024
entrez:
14
6
2024
Statut:
aheadofprint
Résumé
One of the major challenges in the choice of the best therapeutic approach for the treatment of patients affected by hemophilia A (HA) is the definition of criteria predicting the formation of factor VIII (FVIII) neutralizing antibodies, called inhibitors. Both genetic and environmental elements influencing the immune response toward FVIII have been identified but still not all the factors causing the pathological rejection of FVIII have been identified. Since there is a connection between coagulation and inflammation, here we assessed the role played by the FVIII deficiency in shaping the humoral and cellular response toward an antigen other than FVIII itself. To this aim, we challenged both HA and wild-type (WT) mice with either FVIII or ovalbumin (OVA) and followed antigen-specific antibody level, immune cell population frequency and phenotype up to 9 weeks after the last antigen booster. The activation threshold was evaluated in vitro by stimulating the murine T cells with a decreasing dose of α-CD3. The humoral response to FVIII was similar between the two groups while both the in vivo and in vitro experiments highlighted an antigen-independent sensitivity of HA compared with WT T cells causing an increase in memory T-cell conversion and proliferation capability.
Identifiants
pubmed: 38873896
doi: 10.1002/eji.202350807
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2350807Subventions
Organisme : Fondazione Telethon
ID : GGP19201
Organisme : European Union's Horizon 2020 Hemacure
ID : 667421
Organisme : Fondazione Cariplo
ID : 2018-0253
Informations de copyright
© 2024 Wiley‐VCH GmbH.
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