Programmed Death-1 Restrains the Germinal Center in Type 1 Diabetes.

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.

SUBMITTER: Martinov T 

PROVIDER: S-EPMC7083260 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature