Activation marker expression and apoptotic susceptibility of T-cell clones derived from CD34(+), young and SENIEUR donors

Exp Gerontol. 2004 Apr;39(4):531-8. doi: 10.1016/j.exger.2003.11.015.

Abstract

T-cell clones (TCC) derived from human peripheral blood lymphocytes of a young control, a healthy elderly (SENIEUR) donor, or from CD34(+) hematopoietic progenitor cells were utilised in this study to examine how in vivo and in vitro ageing affects T-cell apoptotic capability. The role of CD25, CD28 and the intracellular proteins, FLICE-inhibitory protein (FLIP), receptor-interacting protein (RIP) and caspase 3 were investigated. We observed an age-related decline in the expression of the IL-2 receptor alpha chain CD25, and absence of the co-stimulatory receptor CD28 on three of the four TCC studied. In young donor- and CD34 cell-derived TCC, but not in SENIEUR donor-derived TCC, we observed an age-related increase in susceptibility of the cells to mFas-L-induced apoptosis, which correlated with the age-related decrease of CD25 expression. Expression levels of full-length RIP and FLIP did not show any correlation to apoptotic susceptibility. However, expression levels of the cleaved form of RIP were greatly reduced in the SENIEUR donor-derived TCC, which together with a trend towards increased caspase 3 activity, could indicate an age-related alteration in utilisation of different apoptotic signalling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / immunology*
  • Antigens, CD34 / analysis*
  • Apoptosis / immunology*
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CD28 Antigens / metabolism
  • Carrier Proteins / metabolism
  • Caspase 3
  • Caspases / metabolism
  • Cells, Cultured
  • Cellular Senescence / immunology
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Lymphocyte Activation / physiology*
  • Proteins / metabolism
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Receptors, Interleukin-2 / metabolism
  • Signal Transduction / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Antigens, CD34
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CD28 Antigens
  • CFLAR protein, human
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • Receptors, Interleukin-2
  • RIPK1 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • CASP3 protein, human
  • Caspase 3
  • Caspases