Age-dependent signature of metallothionein expression in primary CD4 T cell responses is due to sustained zinc signaling.

ABSTRACT: The ability to mount adaptive immune responses to vaccinations and viral infections declines with increasing age. To identify mechanisms leading to immunosenescence, primary CD4 T cell responses were examined in 60- to 75-year-old individuals lacking overt functional defects. Transcriptome analysis indicated a selective defect in zinc homeostasis. CD4 T cell activation was associated with zinc influx via the zinc transporter Zip6, leading to increased free cytoplasmic zinc and activation of negative feedback loops, including the induction of zinc-binding metallothioneins. In young adults, activation-induced cytoplasmic zinc concentrations declined after 2 days to below prestimulation levels. In contrast, activated naïve CD4 T cells from older individuals failed to downregulate cytoplasmic

SUBMITTER: Lee WW 

PROVIDER: S-EPMC2848531 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature