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Dissertation
Age-associated changes in influenza A virus-specific CD8-positive lymphocyte responses in C57BL/6 mice
Doctor of Philosophy (Ph.D.), Medical College of Pennsylvania and Hahnemann University
Aug 2001
DOI:
https://doi.org/10.17918/00008946
Abstract
The objective of influenza vaccine is the generation of neutralizing antibodies that will block infection by binding to influenza virus proteins that are required for virus entry into host cells. In the event that antibodies do not neutralize all influenza virus particles, infection will occur and will require cytotoxic T lymphocytes (CTLs) to kill infected cells. The goal of this project was to determine if the age-associated decrease in influenza-specific CTL responses was due to a quantitative defect in virus-specific CD8+ T cells. Young (6mo) and old (22mo) C57BL/6 mice were infected with influenza A virus and assessed either during a primary infection or during a secondary virus infection subsequent to immunization. Using MHC tetramers loaded with the immunodominant nucleoprotein (NP) peptide from influenza A virus, we examined the frequency of virusspecific CD8+ pulmonary T cells and their qualitative expression of various activation markers using flow cytometry. In addition, we assessed effector function using cytotoxicity assays and intracellular interferon (IFN-[gamma]) production. Even though we observed a correlation between lung and spleen in virus-specific lymphocytes expressing the activation marker, CD25 and the phenotype associated with immunological memory, CD44hi/CD62Llo, there was no correlation in either the percentage of influenza-specific CD8+ lymphocytes or cytotoxic activity between spleen and lung of individual infected animals. Collectively, our observations demonstrate that virus-specific CD8+ lymphocyte responses in the spleen do not reflect the responses in the lungs of mice infected with influenza A virus, and highlights the importance of assessing immune responses at the site of infection as opposed to locations distant from the local response. We determined that the age-associated decrease in virus-specific CTL activity was associated with a decrease and a delay in the expansion of virus-specific CD8+ T cells during primary influenza infection. Importantly, qualitative examination of CD8+ T cells during primary influenza infection showed that virus-specific CD8+ lymphocytes from young and old mice were phenotypically similar, in the percent expression of the costimulatory receptor, CD28, the activation marker, CD25, and the CD44hi/CD62Llo phenotype. (Abstract shortened by UMI.).
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Details
- Title
- Age-associated changes in influenza A virus-specific CD8-positive lymphocyte responses in C57BL/6 mice
- Creators
- John Leander Zapanta Po
- Contributors
- Donna Murasko (Advisor) - Drexel University, Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)
- Awarding Institution
- Medical College of Pennsylvania and Hahnemann University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Medical College of Pennsylvania and Hahnemann University; Philadelphia, Pennsylvania
- Number of pages
- xvii, 175 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)
- Other Identifier
- 991021888887804721