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| Status |
Public on Mar 20, 2021 |
| Title |
Resident memory T cells form during persistent antigen exposure leading to allograft rejection |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Tissue resident memory T cells (TRM) contained at sites of previous infection provide local protection against re-infection. Whether they form and function in organ transplants where cognate antigen persists is unclear. This is a key question in transplantation as T cells are detected long-term in allografts, but it is not known whether they are exhausted or are functional memory T cells. Using a mouse model of kidney transplantation, we showed that antigen-specific and polyclonal effector T cells differentiated in the graft into TRM and subqeuntly caused allograft rejection. TRM identity was established by surface phenotype, transcriptional profile, and inability to recirculate in parabiosis and re-transplantation experiments. Graft TRM proliferated locally, produced IFNγ upon re-stimulation, and their in vivo depletion attenuated rejection. Importantly, the vast majority of antigen-specific and polyclonal TRM lacked phenotypic and transcriptional exhaustion markers. Single cell analysis of graft T cells early and late after transplantation identified a transcriptional program associated with transition to the tissue resident state that could serve as a platform for the discovery of therapeutic targets. Thus, recipient effector T cells differentiate into functional graft TRM that maintain rejection locally. Targeting these TRM could improve renal transplant outcomes.
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| Overall design |
Single Cell RNA sequencing of graft infiltrating OT-I and polyclonal T cells early and late after transplantation of OVA expressing allogeneic kidneys in mice
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| Contributor(s) |
Abou-Daya KI, Oberbarnscheidt MH, Lakkis FG |
| Citation(s) |
33741656 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 AI049466 |
T Cell Memory in Organ Transplantation |
UNIVERSITY OF PITTSBURGH AT PITTSBURGH |
Fadi G. Lakkis |
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| |
| Submission date |
Feb 04, 2021 |
| Last update date |
Apr 13, 2021 |
| Contact name |
Khodor I Abou-Daya |
| E-mail(s) |
kha17@pitt.edu
|
| Organization name |
Starzl Transplantation Institute
|
| Department |
Surgery
|
| Street address |
200 Lothrop Street
|
| City |
Pittsburgh |
| State/province |
PA |
| ZIP/Postal code |
15213 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA699537 |
| SRA |
SRP304729 |
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