The role of virus-specific human T cells in influenza A virus infection

Abstract

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.