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| Status |
Public on Apr 23, 2019 |
| Title |
Tolerance Induction in Diabetogenic BDC-2.5 T cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
CD4 T cells play a critical role in promoting the development of autoimmunity in Type 1 Diabetes (T1D). The diabetogenic CD4 T cell clone BDC-2.5, originally isolated from a non-obese diabetic (NOD) mouse, has been widely used to study the contribution of autoreactive CD4 T cells and relevant antigens to autoimmune diabetes. Recent work from our lab has shown that the antigen for BDC-2.5 T cells is a hybrid insulin peptide (2.5HIP) consisting of an insulin C-peptide fragment fused to a peptide from chromogranin A (ChgA), and that endogenous 2.5HIP-reactive T cells are major contributors to autoimmune pathology in NOD mice. The objective of this study was to determine if poly(lactide-co-glycolide) (PLG) nanoparticles (NPs) loaded with the 2.5HIP antigen (2.5HIP-PLG) can tolerize BDC-2.5 T cells. Infusion of 2.5HIP-PLG NPs was found to prevent diabetes in an adoptive transfer model by impairing the ability of BDC-2.5 T cells to produce pro-inflammatory cytokines through induction of anergy, leading to an increase in the ratio of Foxp3+ regulatory T cells to IFN-γ+ effector T cells. This work is the first to use a hybrid insulin peptide, or any neoepitope, to re-educate diabetogenic T cells and may have significant implications for the development of an antigen-specific therapy for T1D patients.
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| Overall design |
Sequencing of FACS-sorted BDC-2.5 TCR-transgenic, CD4-positive, Foxp3-negative (GFP-negative) effector T cells (Teffs) was performed in order to determine the mechanisms of tolerance induction. Activated BDC-2.5 T cells were adoptively transferred into NOD.scid mice and Teffs were sorted from spleen/lymph nodes of 2.5HIP-PLG treated or untreated mice (pooled from 4 mice per group) 6 days after T cell transfer. RNA-Seq data are from 1 experiment without replicates. An up-regulation of anergy related genes in tolerized Teffs was found.
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| Contributor(s) |
Jamison BL, Neef T, Goodspeed A, Bradley B, Baker RL, Miller SD, Haskins K |
| Citation(s) |
31109955 |
| Submission date |
Feb 14, 2019 |
| Last update date |
Jul 23, 2019 |
| Contact name |
Braxton L Jamison |
| E-mail(s) |
braxton.jamison@ucdenver.edu
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| Organization name |
University of Colorado School of Medicine
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| Department |
Department of Immunology and Microbiology
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| Lab |
Kathryn Haskins
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| Street address |
12800 East 19th Avenue Mail Stop 8333
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| City |
Aurora |
| State/province |
CO |
| ZIP/Postal code |
80045 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA522356 |
| SRA |
SRP185879 |
