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

Lee, W.-W., Cui, D., Czesnikiewicz-Guzik, M. , Vencio, R.Z.N., Shmulevich, I., Aderem, A., Weyand, C.M. and Goronzy, J.J. (2009) Age-dependent signature of metallothionein expression in primary CD4 T cell responses is due to sustained zinc signaling. Rejuvenation Research, 11(6), pp. 1001-1011. (doi: 10.1089/rej.2008.0747)

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 zinc, resulting in excessive induction of metallothioneins. Activation-induced metallothioneins regulated the redox state in activated T cells and accounted for an increased proliferation of old CD4 T cells, suggesting that regulation of T cell zinc homeostasis functions as a compensatory mechanism to preserve the replicative potential of naïve CD4 T cells with age.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Czesnikiewicz-Guzik, Dr Marta
• Authors: Lee, W.-W., Cui, D., Czesnikiewicz-Guzik, M., Vencio, R.Z.N., Shmulevich, I., Aderem, A., Weyand, C.M., and Goronzy, J.J.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
• Journal Name: Rejuvenation Research
• ISSN: 1549-1684
• ISSN (Online): 1557-8577