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

  • Martinov T
  • Swanson L
  • Breed E
  • et al.
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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 peptide:MHC class II complex. This work provides an explanation for autoimmune side effects following PD-1 pathway inhibition and suggests that targeting the self-peptide:MHC class II complex might limit autoimmunity arising from checkpoint blockade.

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CITATION STYLE

APA

Martinov, T., Swanson, L. A., Breed, E. R., Tucker, C. G., Dwyer, A. J., Johnson, J. K., … Fife, B. T. (2019). Programmed Death-1 Restrains the Germinal Center in Type 1 Diabetes. The Journal of Immunology, 203(4), 844–852. https://doi.org/10.4049/jimmunol.1801535

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