Unknown

Dataset Information

0

T-cell responses to hybrid insulin peptides prior to type 1 diabetes development.


ABSTRACT: T-cell responses to posttranslationally modified self-antigens are associated with many autoimmune disorders. In type 1 diabetes, hybrid insulin peptides (HIPs) are implicated in the T-cell-mediated destruction of insulin-producing β-cells within pancreatic islets. The natural history of the disease is such that it allows for the study of T-cell reactivity prior to the onset of clinical symptoms. We hypothesized that CD4 T-cell responses to posttranslationally modified islet peptides precedes diabetes onset. In a cohort of genetically at-risk individuals, we measured longitudinal T-cell responses to native insulin and hybrid insulin peptides. Both proinflammatory (interferon-γ) and antiinflammatory (interluekin-10) cytokine responses to HIPs were more robust than those to native peptides, and the ratio of such responses oscillated between pro- and antiinflammatory over time. However, individuals who developed islet autoantibodies or progressed to clinical type 1 diabetes had predominantly inflammatory T-cell responses to HIPs. Additionally, several HIP T-cell responses correlated to worsening measurements of blood glucose, highlighting the relevance of T-cell responses to posttranslationally modified peptides prior to autoimmune disease development.

SUBMITTER: Mitchell AM 

PROVIDER: S-EPMC8017940 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC6702640 | biostudies-literature
| S-EPMC9365947 | biostudies-literature
| S-EPMC8387461 | biostudies-literature
| S-EPMC10487141 | biostudies-literature
| S-EPMC4183919 | biostudies-literature
| S-EPMC4394309 | biostudies-literature
| S-EPMC8435627 | biostudies-literature
2002-12-17 | GSE121 | GEO
| S-EPMC4725668 | biostudies-literature
| S-EPMC3428068 | biostudies-literature