Human influenza-specific effector and memory CD8 T cells from older adults show signs of terminal differentiation and senescence (104.3)

Abstract

Abstract Little is known about normal human aging and its effects on the function of T cells specific for acutely infecting pathogens. To address this issue, we conducted a multicolour flow cytometry study of older persons’ responses to influenza virus challenge ex vivo. Young and elderly donors were recruited in the fall of 2008. PBMCs were stained directly ex vivo or stimulated with A/Puerto Rico/8/34 (PR8) for 18 hours and assessed for functional markers. The data show that most donors have pre-existing influenza-specific T cells (measured by IFNγ) that are reactivated by PR8, although older donors had smaller pre-vaccination populations of flu-responsive T cells. Effector cells identified upon restimulation with influenza displayed a more terminally differentiated phenotype in older compared to younger adults. This phenotype did not change post-vaccination with trivalent inactivated vaccine, which lacks significant internal viral proteins and is a poor inducer of CD8 T cell responses. For HLA-A2+ donors, it was determined by tetramer staining that elderly influenza-specific CD8 T cells express higher levels of senescence markers KLRG1 and CD57 compared to young controls. Our study shows that influenza specific effector and memory T cells from older individuals show signs of terminal differentiation and senescence. Thus, as has been shown for persistent life-long infections, memory CD8 T cells to an acutely infecting pathogen show signs of deterioration with age.