Poor anti-viral immunity in aged mice is associated with defects in CD8 T cell recall responses (44.5)

Abstract

Abstract Aging leads to an increased susceptibility to infectious diseases. To investigate the age-related changes in T cell memory we compared anti-viral CD8 T cell immunity in young versus aged mice following systemic (lymphocytic choriomeningitis virus; LCMV) or local (influenza virus) viral infections. The number of memory CD8 T cells formed was similar or only modestly different between aged and young animals, though in some cases changes in immunodominance and cytokine production were apparent. Both influenza virus-specific and LCMV-specific memory CD8 T cells from aged mice, however, had major substantially reduced proliferative capacity upon secondary infection. As a result, aged mice displayed increased morbidity and mortality upon viral rechallenge. The studies described herein demonstrate that the defects intrinsic to aged CD8 T cells are at least partially responsible for diminished immunity of aged mice. Thus, the strategies that accelerate the induction of T cell responses or that overcome proliferative deficiencies may prove beneficial. These studies were funded by grants from AHA, NIH (HHSN266200500030C) and the Ellison Medical Foundation.