Cellular and Molecular Mechanisms Involved with Feline CD8+ T Cell Mediated Anti-FIV Activity
| dc.contributor.advisor | Dr. Wayne Tompkins, Committee Chair | en_US |
| dc.contributor.author | Hewitt, Tracy P. | en_US |
| dc.date.accessioned | 2010-04-02T19:09:58Z | |
| dc.date.available | 2010-04-02T19:09:58Z | |
| dc.date.issued | 2006-03-02 | en_US |
| dc.degree.discipline | Immunology | en_US |
| dc.degree.level | dissertation | en_US |
| dc.degree.name | PhD | en_US |
| dc.description.abstract | A population of activated CD8+ T cells that express the B7.1 (CD80) and B7.2 (CD86) costimulatory molecules and their ligand CTLA4 exist in the blood of asymptomatic FIV-infected cats. As evidence of CD8+ T cell mediated anti-FIV activity, coculture of CD8+ depleted-PBMC with FCD4E cells resulted in a significant increase in FIV p24 levels as compared to total PBMC cocultures. This anti-FIV activity was not overridden by the addition of either rhIL-2 or ConA. All cats were infected either intravenously or vaginally. There was no correlation between the route of infection and the presence of CD8+ T cell-mediated antiviral activity. Nonsuppressor cats had a higher number of viral RNA molecules per milliliter of plasma than the suppressor cats. PBMC from suppressor cats had a higher percentage of CD8+ CD25+ cells as compared to nonsuppressor cats. Both CD8+ CD25+ and CD8+ CD25- subsets inhibited FIV replication. CD8+ cells from suppressor cats also had an increased in the frequency of B7.1+ CD8+ cells with a low expression of the CD8β chain, suggesting that the CD8+ anti-FIV cells express the activation phenotype, CD8+ βlo B7.1+. Depletion of B7.1+ cells from PBMC of suppressor cats resulted in increased viral replication similar to depletion of CD8+ cells. CD8+B7.1+ and CD8+B7.1- subsets cocultured with infected CD4+ T cells revealed that the antiviral activity reside primarily in CD8+ B7.1+ subset. The presence of CD8+ antiviral cells lead to a decrease in the number of FIV RNA molecules per 106 CD4+ T cells in suppressor cats with no appreciable difference in the expression of IL-2 mRNA levels from either group of cats. The results of this study showed a strong correlation between the presence of CD8+ T cell anti-FIV activity, a reduction in viremia, low expression of the CD8β chain and expression of B7.1 costimulatory molecule on CD8+ T cells in suppressor cats suggesting that CD8+ βlo B7.1+ antiviral cells may play a major role in controlling FIV replication in vivo. | en_US |
| dc.identifier.other | etd-11302004-152236 | en_US |
| dc.identifier.uri | http://www.lib.ncsu.edu/resolver/1840.16/5232 | |
| dc.rights | I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to NC State University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. | en_US |
| dc.subject | FIV | en_US |
| dc.subject | CD8+ T cell antiviral activity | en_US |
| dc.subject | suppressor activity | en_US |
| dc.title | Cellular and Molecular Mechanisms Involved with Feline CD8+ T Cell Mediated Anti-FIV Activity | en_US |
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