Signaling Pathways in Aged T Cells - A Reflection of T Cell Differentiation, Cell Senescence and Host Environment

Semin Immunol. 2012 Oct;24(5):365-72. doi: 10.1016/j.smim.2012.04.003. Epub 2012 May 4.

Abstract

With increasing age, the ability of the immune system to protect against new antigenic challenges or to control chronic infections erodes. Decline in thymic function and cumulating antigenic experiences of acute and chronic infections threaten T cell homeostasis, but insufficiently explain the failing immune competence and the increased susceptibility for autoimmunity. Alterations in signaling pathways in the aging T cells account for many of the age-related defects. Signaling threshold calibrations seen with aging frequently built on mechanisms that are operational in T cell development and T cell differentiation or are adaptations to the changing environment in the aging host. Age-related changes in transcription of receptors and signaling molecules shift the balance towards inhibitory pathways, most dominantly seen in CD8 T cells and to a lesser degree in CD4 T cells. Prominent examples are the expression of negative regulatory receptors of the CD28 and the TNF receptor superfamilies as well the expression of various cytoplasmic and nuclear dual-specific phosphatases.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aging
  • Animals
  • Cell Differentiation*
  • Cellular Senescence*
  • Humans
  • Receptors, Antigen, T-Cell / immunology
  • Signal Transduction*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Receptors, Antigen, T-Cell