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Series GSE220447 Query DataSets for GSE220447
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
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.
 
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
 
Contributor(s) Hu M, O'Connell PJ, Gloss BS, Lai J, Zhao Y, Nicholson L, Qian YW
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Submission date Dec 07, 2022
Last update date Mar 22, 2024
Contact name Brian S Gloss
E-mail(s) brian.gloss@sydney.edu.au
Organization name Westmeand Institute of Medical Research
Department Scientific Platforms
Lab Bioinformatics
Street address 176 Hawkesbury Rd
City Westmead
State/province NSW
ZIP/Postal code 2145
Country Australia
 
Platforms (2)
GPL16417 Illumina MiSeq (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (33)
GSM6801886 SP/NaiveCD45+CD4-_1
GSM6801888 SP/NaiveCD45+CD4-_2
GSM6801889 SP/NaiveCD45+CD4-_3
Relations
BioProject PRJNA909782

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE220447_RAW.tar 5.4 Mb (http)(custom) TAR (of TAB)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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