Abstract
BackgroundAgeing has been shown to reduce CD8 T cell repertoire diversity and immune responses against influenza virus infection in mice. In contrast, less is known about the impact of ageing on CD4 T cell repertoire diversity and immune response to influenza virus infection.ResultsThe CD4 T cell response was followed after infection of young and aged C57BL/6 mice with influenza virus using a tetramer specific for an immunodominant MHC class II epitope of the influenza virus nucleoprotein. The appearance of virus-specific CD4 T cells in the lung airways of aged mice was delayed compared to young mice, but the overall peak number and cytokine secretion profile of responding CD4 T cells was not greatly perturbed. In addition, the T cell repertoire of responding cells, determined using T cell receptor Vβ analysis, failed to show the profound effect of age we previously described for CD8 T cells. The reduced impact of age on influenza-specific CD4 T cells was consistent with a reduced effect of age on the overall CD4 compared with the CD8 T cell repertoire in specific pathogen free mice. Aged mice that were thymectomized as young adults showed an enhanced loss of the epitope-specific CD4 T cell response after influenza virus infection compared with age-matched sham-thymectomized mice, suggesting that a reduced repertoire can contribute to impaired responsiveness.ConclusionsThe diversity of the CD4 T cell repertoire and response to influenza virus is not as profoundly impaired by ageing in C57BL/6 mice as previously shown for CD8 T cells. However, adult thymectomy enhanced the impact of ageing on the response. Understanding the impact of ageing on CD4 T cell responses to influenza virus infection is an important prerequisite for developing better vaccines for the elderly.
Highlights
Ageing has been shown to reduce CD8 T cell repertoire diversity and immune responses against influenza virus infection in mice
The epitope-specific CD4 T cell response to influenza virus infection is delayed in aged mice
The impact of ageing on epitope-specific CD4 T cells responding to influenza virus infection in C57BL/6 mice has not previously been determined
Summary
Ageing has been shown to reduce CD8 T cell repertoire diversity and immune responses against influenza virus infection in mice. Less is known about the impact of ageing on CD4 T cell repertoire diversity and immune response to influenza virus infection. It is well-established that ageing is associated with a decline in immune function [1,2]. Thymic involution with age results in the export of fewer naïve T cells to the periphery. This reduction in the influx of naïve T cells, coupled with an increase in memory cells due to accumulating antigen experience, enhanced homeostatic proliferation to compensate for reduced naïve T cell production, peripheral selection, and the development of T cell clonal expansions (TCEs) leads to the progressive dominance of numbers of memory compared to naïve T cells in aged individuals [5,6,7,8,9]. Decline in CD8 T cell repertoire diversity has been clearly associated with impaired responses to new infections, including influenza virus [11,14,15,16,17]
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