Programmed Death-1 Restrains the Germinal Center in Type 1 Diabetes.
J Immunol
; 203(4): 844-852, 2019 08 15.
Article
em En
| MEDLINE
| ID: mdl-31324724
ABSTRACT
Programmed death-1 (PD-1) inhibits T and B cell function upon ligand binding. PD-1 blockade revolutionized cancer treatment, and although numerous patients respond, some develop autoimmune-like symptoms or overt autoimmunity characterized by autoantibody production. PD-1 inhibition accelerates autoimmunity in mice, but its role in regulating germinal centers (GC) is controversial. To address the role of PD-1 in the GC reaction in type 1 diabetes, we used tetramers to phenotype insulin-specific CD4+ T and B cells in NOD mice. PD-1 or PD-L1 deficiency, and PD-1 but not PD-L2 blockade, unleashed insulin-specific T follicular helper CD4+ T cells and enhanced their survival. This was concomitant with an increase in GC B cells and augmented insulin autoantibody production. The effect of PD-1 blockade on the GC was reduced when mice were treated with a mAb targeting the insulin peptideMHC class II complex. This work provides an explanation for autoimmune side effects following PD-1 pathway inhibition and suggests that targeting the self-peptideMHC class II complex might limit autoimmunity arising from checkpoint blockade.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Linfócitos T CD4-Positivos
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Autoimunidade
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Diabetes Mellitus Tipo 1
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Receptor de Morte Celular Programada 1
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2019
Tipo de documento:
Article