 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jun 20, 2024 |
| Title |
Dysfunction of infiltrating cytotoxic CD8+ T cells within the graft promotes murine kidney allotransplant tolerance |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Tolerance of mouse kidney allografts arises in grafts that develop regulatory Tertiary Lymphoid Organs (rTLOs). scRNAseq data and adoptive transfer of alloreactive T cells post-transplant showed that cytotoxic CD8+ T cells are reprogrammed within the accepted graft to an exhausted/regulatory-like phenotype. Establishment of rTLOs was required since adoptive transfer of alloreactive T cells prior to transplantation results in kidney allograft rejection. Despite intragraft CD8+ cells with a regulatory phenotype, they were not essential for the induction and maintenance of kidney allograft tolerance. Analysis of scRNAseq data from allograft kidneys and malignant tumors identified similar regulatory-like cell types within the T cell clusters. Induction of cytotoxic CD8+ T cell dysfunction of infiltrating cells appears to be a beneficial mechanistic pathway that protects the kidney allotransplant from rejection through a process we call “defensive tolerance.” This pathway has implications for our understanding of allotransplant tolerance and tumor resistance to host immunity.
|
| |
|
| Overall design |
Isolated kidney or spleen cells were sorted for viable CD45+ cells via flow cytometry using an anti-CD45+ antibody and a fixable viability dye. These cells were used to construct single-cell RNA-seq libraries at Chromium 10x instrument using Chromium Next GEM Single Cell 3’ kit, which were sequenced in paired-end fashion on Illumina HiSeq 2500 instrument to the depth of approximately 100 million read pairs per sample.
|
| |
|
| Contributor(s) |
Takahiro Y, Edward S, Andrew L, Taisuke B, David R, Michelle P, Alessadnro A |
| Citation(s) |
38888968 |
| |
| Submission date |
Jan 02, 2024 |
| Last update date |
Jun 21, 2024 |
| Contact name |
Alessandro Alessandrini |
| E-mail(s) |
aalessandrini@partners.org
|
| Organization name |
Massachusetts General Hospital
|
| Street address |
55 Fruit Street , WEL 807
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02114 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (16)
|
| GSM7999672 |
Accept kidney allografts, total cells, integrated of 1 & 3 & 24 weeks, scRNAseq |
| GSM7999673 |
Accept recipient spleen, total cells, integrated of 1 & 3 & 24 weeks, scRNAseq |
| GSM7999674 |
Accept kidney grafts, 1 week, total cell, scRNAseq |
| GSM7999675 |
Accept kidney grafts, 3 week, total cell, scRNAseq |
| GSM7999676 |
Accept kidney grafts, 24 week, total cell, scRNAseq |
| GSM7999677 |
Rejecting kidney grafts, 1 week, total cell, scRNAseq |
| GSM7999678 |
Naive spleen, total cell, scRNAseq |
| GSM7999679 |
Accept kidney grafts, 1 week, CD8 T cell, scRNAseq |
| GSM7999680 |
Accept kidney grafts, 3 week, CD8 T cell, scRNAseq |
| GSM7999681 |
Accept kidney grafts, 24 week, CD8 T cell, scRNAseq |
| GSM7999682 |
Accept recipient spleen, 1 week, CD8 T cell, scRNAseq |
| GSM7999683 |
Accept recipient spleen, 3 week, CD8 T cell, scRNAseq |
| GSM7999684 |
Accept recipient spleen, 24 week, CD8 T cell, scRNAseq |
| GSM7999685 |
Rejecting kidney grafts, 1 week, CD8 T cell, scRNAseq |
| GSM7999686 |
Rejecting recipient spleen, 1 week, CD8 T cell, scRNAseq |
| GSM7999687 |
Naive spleen, CD8 T cell, scRNAseq |
|
| Relations |
| BioProject |
PRJNA1060247 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE252337_RAW.tar |
6.1 Gb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
|
|
|
|
 |
Less...
More...