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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 30, 2014 |
| Title |
Tolerant and rejecting T cell microarray |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
anti-CD4, CD8 and CD40L treated versus control murine CD4+ T cells from micegrafted with hESC derived xenografts.
Human embryonic stem cells (ESCs), by virtue of their capability to self-renew and differentiate into almost all body cell types, represent the first type of pluripotent stem cells (PSCs) to be used in clinical transplantation to humans in recent phase-I trials. As it is unlikely that any such cells or their progeny will survive in an allogeneic host, there is an urgent need to understand how to get long-term acceptance and functional differentiation with minimal immunosuppression. Here, we show that brief induction with combined monoclonal antibody-mediated coreceptor and costimulation blockade enables long-term survival and engraftment of murine ESCs, human ESCs, human induced PSCs, and human ESC-derived progenitor cells from all three embryonic germ layers. Tolerance induced to PSC-derived progenitors appears, remarkably, to extend to protection of their differentiated progenies, and sometimes even to different tissues derived from the same donor, suggesting linked-suppression as a likely operative mechanism. These results suggest that once tolerance has been established to PSC-derived progenitor cells, it can be extended to their differentiated progenies. Global gene expression profiling of graft infiltrating T-lymphocytes identifies gene sets that differ between rejecting and tolerant populations including gene upregulation in pathways associated with apoptosis, cell adhesion, transcription suppression and TGF synthesis; and gene downregulation in pathways associated with inflammation in recipients treated with combined coreceptor and costimulation blockade.
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| Overall design |
Mice grafted with hESC derived tissues and untreated (control) or tolerised via injections of anti-CD4, anti CD8 and CD40L. CD3+ T cells isolated from the gratfs 30 days later.
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| Contributor(s) |
Howie D, Lui KO |
| Citation(s) |
25434740 |
| Submission date |
Sep 29, 2014 |
| Last update date |
Apr 18, 2017 |
| Contact name |
Duncan Howie |
| Organization name |
Oxford University
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| Department |
Sir William Dunn School of Pathology
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| Lab |
Therapeutic Immunology Group
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| Street address |
South Parks Road
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| City |
Oxford |
| State/province |
Oxon |
| ZIP/Postal code |
OX1 3RE |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL11533 |
[MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA262573 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE61867_RAW.tar |
25.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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