Influenza A virus infection is a major cause of human morbidity and mortality. T cell
immunity is believed to play critical roles for host defenses against influenza A infection.
Once intracellular influenza A infection is established, viral clearance is mainly dependent on
virus-specific CD8+ T cells. CD4+ T cells are important for adaptive immunity to natural
influenza A infection or vaccination by providing help to B cells for antibody production and
also providing help to CD8+ T cells for the generation of cytotoxicity. In addition, virusspecific
CD4+ and CD8+ T cells are rich sources of effector cytokines, such as IFN-and
TNF-, which can promote the function of antigen presenting cells and have direct antiviral
activity. Cross-subtype reactive CD4+ and CD8+ memory T cells also affect the clearance of
virus infection even in those who lack virus-specific antibodies. Therefore, the aim of our
study is to assess the influenza virus-specific T cell responses and define their possible
protective role in pandemic H1N1 virus and seasonal influenza infection in human.
First we determined whether healthy adults have the cross-reactivity of memory CD4+ and
CD8+ T cells against pandemic virus. In April of 2009, 7 pandemic H1N1 infected patients
and 17 their healthy contacts who had no pandemic influenza infection were recruited in this
study. By using intracellular IFN-staining and flow cytometry, we examined their pandemic
H1N1 virus and seasonal influenza H1N1-specific CD4+ and CD8+ T cell responses. Healthy
contacts did have measurable but low frequencies of cross-reactive influenza-specific CD4+
and CD8+ T cells, though the frequencies of these T cells specific to pandemic H1N1 virus
were slightly lower than that specific to seasonal H1N1 virus. Furthermore, when compared
the pandemic H1N1-specific T cell responses between healthy contacts and patients with
pandemic H1N1 infection, we can found that the healthy contacts have higher pandemic
H1N1 specific-T cell responses than patients, suggesting these pre-existing pandemic H1N1
specific-T cells may have protection from pandemic influenza virus infection.
In addition, we conducted a prospective T cell immunity and influenza surveillance study in a
cohort of more than 200 healthy volunteers before the influenza season and investigated
whether the pre-existing T cell immunity is related to the protection from influenza infection
in the next coming influenza season. Using intracellular IFN-staining assay, we examined
their pre-existing seasonal influenza H1N1, H3N2, seasonal influenza B virus-specific CD4+
and CD8+ T cell responses. Due to the small number of cases of influenza infection in the
coming influenza season, the results only showed a trend that the subjects who have higher
frequency of influenza virus strain-specific T cells may have lower chance to suffer from
same strain of influenza infection, which to some extent, reflect the pre-exist memory T cells
have association with the protection in the coming influenza season.
In conclusion, T cells play an important role in defensing against influenza infection. The
higher influenza virus specific-T cells response activity in healthy adults may have a
protection against influenza virus infection. / published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Philosophy
| Identifer | oai:union.ndltd.org:HKU/oai:hub.hku.hk:10722/208423 |
| Date | January 2011 |
| Creators | Guan, Jing, 管静 |
| Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
| Source Sets | Hong Kong University Theses |
| Language | English |
| Detected Language | English |
| Type | PG_Thesis |
| Rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works., Creative Commons: Attribution 3.0 Hong Kong License |
| Relation | HKU Theses Online (HKUTO) |
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