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| Status |
Public on Mar 22, 2024 |
| Title |
Intragraft memory-like CD127hiCD4+Foxp3+ regulatory T cells maintain transplant tolerance |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
CD4+Foxp3+ regulatory T cells (Tregs) play an essential role in suppressing transplant rejection but their role within the graft, is poorly understood. To address this, we compared phenotypic and transcriptomic characteristics of Treg populations within lymphoid-organs and grafts in an islet xenotransplant model of tolerance induced by co-stimulation blockade. In this study, Tregs were essential for tolerance induction and their numbers increased over time. Tregs demonstrated phenotypic and transcriptional heterogeneity within the graft, and lymphoid organs of tolerant mice. A sub-population of CD127highTreg with memory-like and suppressive features were present in high proportions within long surviving islet-grafts of tolerant mice and had a transcriptomic profile consistent with tissue-Tregs. Importantly these CD127highTregs were better able to prevent rejection by effector T cells, after adoptive transfer into secondary Rag-/- hosts, than naïve Tregs, or unselected Tregs isolated from tolerant mice. We propose that after initial development within the draining lymph node they undergo further genetic reprogramming within the graft towards a phenotype that has shared characteristics with other tissue or tumour Tregs. These findings provide a new focus for engineering such cells either in vivo or for adoptive transfer for inducing tolerance.
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| Overall design |
To determine if there were distinctive molecular profiles for memory-like CD127highTregs and graft-Tregs in this transplant tolerant model, and to explored possible precursor relationships between secondary lymphoid-organ Tregs and non-lymphoid tissue-Tregs, as well as among CD127highTregs, CD127-/lowTregs, graft-Tregs and naïve-Tregs
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| Contributor(s) |
Hu M, O'Connell PJ, Gloss BS, Lai J, Zhao Y, Nicholson L, Qian YW |
| Citation(s) |
38516885 |
| |
| Submission date |
Dec 07, 2022 |
| Last update date |
May 24, 2024 |
| Contact name |
Brian S Gloss |
| E-mail(s) |
brian.gloss@sydney.edu.au
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| Organization name |
Westmead Institute of Medical Research
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| Department |
Scientific Platforms
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| Lab |
Bioinformatics
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| Street address |
176 Hawkesbury Rd
|
| City |
Westmead |
| State/province |
NSW |
| ZIP/Postal code |
2145 |
| Country |
Australia |
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| Platforms (2) |
| GPL16417 |
Illumina MiSeq (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (33)
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| Relations |
| BioProject |
PRJNA909782 |
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