Unknown

Dataset Information

0

Increased Effector Memory Insulin-Specific CD4+ T Cells Correlate With Insulin Autoantibodies in Patients With Recent-Onset Type 1 Diabetes.


ABSTRACT: Type 1 diabetes (T1D) results from T cell-mediated destruction of insulin-producing β-cells. Insulin represents a key self-antigen in disease pathogenesis, as recent studies identified proinsulin-responding T cells from inflamed pancreatic islets of organ donors with recent-onset T1D. These cells respond to an insulin B-chain (InsB) epitope presented by the HLA-DQ8 molecule associated with high T1D risk. Understanding insulin-specific T-cell frequency and phenotype in peripheral blood is now critical. We constructed fluorescent InsB10-23:DQ8 tetramers, stained peripheral blood lymphocytes directly ex vivo, and show DQ8+ patients with T1D have increased tetramer+ CD4+ T cells compared with HLA-matched control subjects without diabetes. Patients with a shorter disease duration had higher frequencies of insulin-reactive CD4+ T cells, with most of these cells being antigen experienced. We also demonstrate that the number of insulin tetramer+ effector memory cells is directly correlated with insulin antibody titers, suggesting insulin-specific T- and B-cell interactions. Notably, one of four control subjects with tetramer+ cells was a first-degree relative who had insulin-specific cells with an effector memory phenotype, potentially representing an early marker of T-cell autoimmunity. Our results suggest that studying InsB10-23:DQ8 reactive T-cell frequency and phenotype may provide a biomarker of disease activity in patients with T1D and those at risk.

SUBMITTER: Spanier JA 

PROVIDER: S-EPMC5697953 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC10281076 | biostudies-literature
| S-EPMC5572390 | biostudies-literature
| S-EPMC9732547 | biostudies-literature
| S-EPMC4370324 | biostudies-literature
| S-EPMC7396835 | biostudies-literature
| S-EPMC10849707 | biostudies-literature
| S-EPMC8829513 | biostudies-literature
| S-EPMC10350289 | biostudies-literature
| S-EPMC5355363 | biostudies-literature