Establishing a comprehensive and dynamic map of the alloimmune response in solid organ transplantation
Abstract/Contents
- Abstract
- The dynamic and multi-dimensional properties of our immune system that makes it so remarkable are the same properties that cause us problems in solid-organ transplantation and causes acute rejection. Our immune system views genetically different tissue of the transplanted organ as a dangerous foreign substance similar to a pathogen and attacks it. The ongoing challenge is to determine how we can circumvent the natural defense mechanisms of the immune system without sacrificing its numerous regulatory functions. The datasets described in this thesis address this challenge by applying high-dimensional cytometry analysis to deep profile the peripheral immune cells involved in acute rejection using a murine model of transplantation. More than 40 different markers are used to obtain a highly granular and multi-parametric proteomic overview of the immune signature that defines acute rejection. This analysis is performed in spleen and lymph node over multiple days post-transplant from day 1 to day 7. T cells, NK cells, monocytes, macrophages, and dendritic cells are expansively profiled to ascertain the differences in protein composition that associate with acute rejection. This high resolution characterization of the immune response reveals a unique phenotypic signature of rejection that is evident by day 5 post-transplantation, and clearly distinguishes rejecting from non-rejecting grafts. This alloimmune phenotype is furthermore conserved across two distinct models of acute rejection. Lastly, strategies to prolong allograft survival are investigated with the use of plasmacytoid dendritic cells (pDC). The results reported here reveal tolerogenic properties that are unique to pDC when compared to conventional dendritic cells. The molecular profile of these pDC points to a potential mechanism of harnessing the immune system's natural immune suppressive capabilities to prolong graft survival. Taken together, these data provide a comprehensive and dynamic map of the alloimmune response in solid organ transplant and provides a foundation for unveiling new therapeutic strategies that can effectively delay graft rejection.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Harden, James Terrell |
|---|---|
| Degree supervisor | Krams, Sheri Michele |
| Thesis advisor | Krams, Sheri Michele |
| Thesis advisor | Bendall, Sean, 1979- |
| Thesis advisor | Idoyaga, Juliana |
| Degree committee member | Bendall, Sean, 1979- |
| Degree committee member | Idoyaga, Juliana |
| Associated with | Stanford University, Department of Microbiology and Immunology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | James Harden. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/ct259fz7496 |
Access conditions
- Copyright
- © 2022 by James Terrell Harden
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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