Unknown

Dataset Information

0

Attenuated IL-2R signaling in CD4 memory T cells of T1D subjects is intrinsic and dependent on activation state.

ABSTRACT: The IL-2/IL-2R pathway is implicated in type 1 diabetes (T1D). While its role in regulatory T cell (Treg) biology is well characterized, mechanisms that influence IL-2 responses in effector T cells (Teff) are less well understood. We compared IL-2 responses in 95 healthy control and 98 T1D subjects. In T1D, low IL-2 responsiveness was most pronounced in memory Teff. Unlike Treg, CD25 expression did not influence the Teff responses. Reduced IL-2 responses in memory Teff were not rescued by resting, remained lower after activation and proliferation, and were absent in type 2 diabetes. Comparing basal IL-2 responses in resting versus activated cells, memory Teff displayed lower, but more sustained, responses to IL-2 overtime. These results suggest that T1D-associated defects in the Teff compartment are due to intrinsic factors related to activation. Evaluation of both Teff and Treg IL-2R signaling defects in T1D subjects may inform selection of therapies.

SUBMITTER: Schwedhelm K 

PROVIDER: S-EPMC5564451 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Attenuated IL-2R signaling in CD4 memory T cells of T1D subjects is intrinsic and dependent on activation state.

Schwedhelm Katharine K   Thorpe Jerill J   Murray Sara A SA   Gavin Marc M   Speake Cate C   Greenbaum Carla C   Cerosaletti Karen K   Buckner Jane J   Long S Alice SA  

Clinical immunology (Orlando, Fla.) 20170620

The IL-2/IL-2R pathway is implicated in type 1 diabetes (T1D). While its role in regulatory T cell (Treg) biology is well characterized, mechanisms that influence IL-2 responses in effector T cells (Teff) are less well understood. We compared IL-2 responses in 95 healthy control and 98 T1D subjects. In T1D, low IL-2 responsiveness was most pronounced in memory Teff. Unlike Treg, CD25 expression did not influence the Teff responses. Reduced IL-2 responses in memory Teff were not rescued by restin  ...[more]

Similar Datasets

Unknown T cell-intrinsic IL-1R signaling licenses effector cytokine production by memory CD4 T cells.
| S-EPMC6085393 | biostudies-literature
Unknown Intrinsic resting-state activity predicts working memory brain activation and behavioral performance.
| S-EPMC6870161 | biostudies-literature
Unknown IL-2R? abundance differentially tunes IL-2 signaling dynamics in CD4+ and CD8+ T cells.
| S-EPMC5741096 | biostudies-literature
Unknown Defects in IL-2R signaling contribute to diminished maintenance of FOXP3 expression in CD4(+)CD25(+) regulatory T-cells of type 1 diabetic subjects.
| S-EPMC2809970 | biostudies-literature
Unknown Cutting Edge: Activation-Induced Iron Flux Controls CD4 T Cell Proliferation by Promoting Proper IL-2R Signaling and Mitochondrial Function.
| S-EPMC7329364 | biostudies-literature
Unknown Pre-diagnostic genotyping identifies T1D subjects with impaired Treg IL-2 signaling and an elevated proportion of FOXP3+IL-17+ cells.
| S-EPMC5843473 | biostudies-literature
Unknown Antiviral CD4+ memory T cells are IL-15 dependent.
| S-EPMC2118539 | biostudies-literature
Unknown An autoimmune-associated variant in PTPN2 reveals an impairment of IL-2R signaling in CD4(+) T cells.
| S-EPMC3058680 | biostudies-literature
Unknown A composite immune signature parallels disease progression across T1D subjects.
| S-EPMC6962023 | biostudies-literature
Transcriptomics Memory CD4+ T cells from Vaccinia vaccinated subjects.
2017-10-01 | GSE60920 | GEO