The immune system must be able to mount a response against pathogens and transformed cells while remaining tolerant to healthy host tissue. A key process for ensuring this self-tolerance is the negative selection of self-reactive
thymocytes. Expression of Programmed Death-1 (PD-1), a co-inhibitory member of the CD28 family associated with dampened peripheral immune responses,was found to be upregulated in 20-40% of thymocytes undergoing negative
selection in the HYcd4model of thymic development. Although analysis of gene and protein expression directly ex vivo indicates that PD-1- and PD-1+ thymocytes are equally apoptotic, PD-1+ thymocytes appear to be protected from
apoptosis in an in vitro stimulation assay. Analysis of HYcd4PD-1-/- mice indicates that thymocytes receive a higher intensity signal in the absence of PD-1. Future work utilizing HYcd4PD-1-/- mice will increase our understanding of the role of PD-1 in thymic negative selection. / Immunology
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:AEU.10048/1654 |
| Date | 06 1900 |
| Creators | Parkman, Julia C |
| Contributors | Baldwin, Troy (Medical Microbiology and Immunology), Ostergaard, Hanne (Medical Microbiology and Immunology), Anderson, Colin (Surgery), Ingham, Robert (Medical Microbiology and Immunology) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 9656513 bytes, application/pdf |
| Relation | Hu, Q., A. Sader, J. C. Parkman, and T. A. Baldwin. 2009. Bim-mediated apoptosis is not necessary for thymic negative selection to ubiquitous self-antigens. J Immunol 183:7761-7767. |
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