Signal transduction changes in CD4+ and CD8+ T cell subpopulations with aging

Exp Gerontol. 2018 May:105:128-139. doi: 10.1016/j.exger.2018.01.005. Epub 2018 Jan 5.

Abstract

The innate and adaptive branches of the immune system display changes with aging, a fact referred to as immunosenescence. Furthermore, it has been established that adaptive immunity is more susceptible to age-related changes than innate immunity. The most prominent phenotypic changes that reflect the specific differentiation and role of each T cell subpopulation are two-fold. They are a decreased number of naïve T cells that parallels an increase in memory T cells, mainly in the cytotoxic CD8+ T cell population, which can be subdivided into naïve, central, effector memory and TEMRA cells. The two main T cell properties that are the most affected with aging are the altered clonal expansion and decreased cytokine production, especially IL-2. These T cell functions have been shown to be affected in the early events of signaling. The aim of the present study was to investigate the influence of age on TCR- and CD28-dependent activation of the downstream signaling effectors Lck, SHP-1, Akt, PI3K p85α and mTOR in differentiated subpopulations of CD4+ and CD8+ T cells. Results showed that lymphocytes of elderly subjects were already in an activated state that could not be upregulated by external stimulation. Results also showed that the age-related signal transduction changes were more important than phenotype in the CD4+ and CD8+ T subpopulations. These observations suggested that age-related molecular and biochemical changes have a more significant influence on T cell functions than T cell phenotype.

Keywords: CD4(+) T cell subpopulations; CD4(+) T cells; CD8(+) T cell subpopulations; CD8(+) T cells; Signal transduction; T cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aging / immunology*
  • CD28 Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Female
  • Healthy Volunteers
  • Humans
  • Immunity, Innate
  • Lymphocyte Activation
  • Male
  • Signal Transduction*
  • Young Adult

Substances

  • CD28 Antigens