|
|
QSpace at Queen's University >
Theses, Dissertations & Graduate Projects >
Queen's Theses & Dissertations >
Please use this identifier to cite or link to this item:
http://hdl.handle.net/1974/6701
|
This item is restricted and will be released 2016-08-31.
| Title: | The Influence of 1,25-Dihydroxyvitamin D3 on the Cross-Priming of Lymphocytic Choriomeningitis Virus Nucleoprotein |
| Authors: | Kim, Julia |
|
|
| Keywords: | 1,25-Dihydroxyvitamin D3
Lymphocytic Choriomeningitis Virus Nucleoprotein
Cross presentation
1,25-(OH)2D3
Cross priming |
| Issue Date: | 2-Sep-2011 |
| Series/Report no.: | Canadian theses |
| Abstract: | Biologically active 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) binds the vitamin D receptor (VDR) to exert its effect on target cells. VDR expression is found in a number of immune cells including professional antigen-presenting cells such as dendritic cells. It has been found that the actions of 1,25-(OH)2D3 on the immune system are mainly immunosuppressive. The cross-presentation pathway allows for exogenously derived antigens to be presented by pAPCs on MHC-I molecules to CD8+ T cells. CD8+ T cell activation results in the expansion of epitope-specific T cell populations that confer host protection. These epitopes can be organized into an immunodominance hierarchy. Previous work demonstrated that introducing LCMV-NP via the cross-priming pathway significantly alters the immunodominance hierarchy of a subsequent LCMV infection. Building upon these observations, our study assessed the effects of LCMV-NP cross priming in the presence of a single dose of 1,25-(OH)2D3. Treatment with 1,25-(OH)2D3 was found to have biological effects in our model system. In vitro pAPCs were demonstrated to up-regulate IL-10 and CYP24A1 mRNA, in addition to the transactivation of cellular VDR, as demonstrated by a relocalization to the nuclear region. Mice treated with 1,25-(OH)2D3 were found to produce up-regulated IL-10 and CYP24A1 transcripts. Expression of VDR was increased at both the transcript and protein level. Our results demonstrate that a single dose of 1,25-(OH)2D3 does not affect the cross-priming pathway in this system. Treatment with 1,25-(OH)2D3 did not influence the ability of differentiated pAPCs to phagocytose or cross-present exogenous antigen to epitope-specific CD8+ T cells. Furthermore, 1,25-(OH)2D3 did not alter cross-priming or the establishment of the LCMV immunodominance hierarchy in vivo. By confirming that 1,25-(OH)2D3 does not suppress cross-priming in our model, our study helps to expand the understanding of the immunomodulatory role of exogenous 1,25-(OH)2D3 on the outcome of virus infection. Collectively, our data supports the observation that the role of 1,25-(OH)2D3 in the immune system is not always associated with suppressive effects. |
| Description: | Thesis (Master, Microbiology & Immunology) -- Queen's University, 2011-08-29 14:53:18.766 |
| URI: | http://hdl.handle.net/1974/6701 |
| Appears in Collections: | Queen's Theses & Dissertations
Microbiology & Immunology Graduate Theses
|
Items in QSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
|
