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

• Published in: Experimental gerontology Vol. 105; pp. 128 - 139
• Main Authors: Le Page, Aurélie, Dupuis, Gilles, Larbi, Anis, Witkowski, Jacek M., Fülöp, Tamas
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.05.2018
• Subjects: Adult; Aged; Aging - immunology; CD28 Antigens - immunology; CD4+ T cell subpopulations; CD4+ T cells; CD4-Positive T-Lymphocytes - immunology; CD8+ T cell subpopulations; CD8+ T cells; CD8-Positive T-Lymphocytes - immunology; Cell Differentiation; Female; Healthy Volunteers; Humans; Immunity, Innate; Lymphocyte Activation; Male; Signal Transduction; T cells; Young Adult; CD4+ T cell subpopulations; Signal transduction; CD8+ T cells; CD8+ T cell subpopulations; CD4+ T cells; T cells; CD8(+) T cells; CD8(+) T cell subpopulations; CD4(+) T cell subpopulations; CD4(+) T cells
• ISSN: 0531-5565; 1873-6815; 1873-6815
• DOI: 10.1016/j.exger.2018.01.005

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. •T lymphocytes of elderly subjects are already in an activated state.•Signal transduction changes are more related to age than to the phenotype in the CD4+ and CD8+ T subpopulations.•T cell subpopulations state of differentiation may support their specific role but not their functions with aging.