title: Impact of ageing on the response and repertoire of influenza virus-specific CD4 T cells.
abstract: BACKGROUND
  Ageing 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Trudeau Institute, 154 Algonquin Ave, Saranac Lake, NY 12983, USA.
authors.forename: Kathleen G
authors.initials: KG
authors.lastname: Lanzer
authors.affiliation: Trudeau Institute, 154 Algonquin Ave, Saranac Lake, NY 12983, USA.
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: Johnson
authors.affiliation: Trudeau Institute, 154 Algonquin Ave, Saranac Lake, NY 12983, USA ; Keystone Symposia, 160 US Highway 6, Suite 200, Silverthorne, CO 80498, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Woodland
authors.affiliation: Trudeau Institute, 154 Algonquin Ave, Saranac Lake, NY 12983, USA.
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Blackman
keywords: Ageing; CD4 T cells; Cytokine; Epitope; Influenza virus; Mouse model; T cell receptor repertoire; Thymectomy