Follicular helper T cell profiles predict response to costimulation blockade in type 1 diabetes.
Nat Immunol
; 21(10): 1244-1255, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32747817
ABSTRACT
Follicular helper T (TFH) cells are implicated in type 1 diabetes (T1D), and their development has been linked to CD28 costimulation. We tested whether TFH cells were decreased by costimulation blockade using the CTLA-4-immunoglobulin (Ig) fusion protein (abatacept) in a mouse model of diabetes and in individuals with new-onset T1D. Unbiased bioinformatics analysis identified that inducible costimulatory molecule (ICOS)+ TFH cells and other ICOS+ populations, including peripheral helper T cells, were highly sensitive to costimulation blockade. We used pretreatment TFH profiles to derive a model that could predict clinical response to abatacept in individuals with T1D. Using two independent approaches, we demonstrated that higher frequencies of ICOS+ TFH cells at baseline were associated with a poor clinical response following abatacept administration. Therefore, TFH analysis may represent a new stratification tool, permitting the identification of individuals most likely to benefit from costimulation blockade.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Auxiliares-Indutores
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Antígenos CD28
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Centro Germinativo
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Diabetes Mellitus Tipo 1
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Abatacepte
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Inibidores de Checkpoint Imunológico
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Imunoterapia
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article