Interleukin 2, interleukin 2 receptor, and interferon-gamma synthesis and mRNA expression in phorbol myristate acetate and calcium ionophore A23187-stimulated T cells from elderly humans

Clin Immunol Immunopathol. 1989 Nov;53(2 Pt 1):297-308. doi: 10.1016/0090-1229(89)90058-5.

Abstract

The levels of interleukin 2 (IL-2), interleukin 2 receptor (IL-2R), and interferon-gamma (IFN-gamma) specific mRNA and their gene products were examined in phorbol myristate acetate (PMA) and calcium ionophore A23187-costimulated purified T cells from young and elderly humans. In addition, the number of high-affinity IL-2R per activated cell, the high-affinity IL-2R density, and the proliferative response of the cells were measured. Among PMA/A23187-stimulated T cells, there was no statistically significant age-related difference in IL-2 or IL-2R specific mRNA accumulation or in the amount of IL-2 or IL-2R synthesized. IFN-gamma specific mRNA was increased significantly in T cells from elderly individuals and the amount of IFN-gamma synthesized by PMA/A23187-activated T cells was nearly double that produced by cells from young individuals. Quantification of the number of high-affinity IL-2R by [125I]IL-2 binding demonstrated there was no decrease in either the mean number or the dissociation constant of the high-affinity IL-2R on activated T cells of the elderly. Despite producing large amounts of IL-2 and having comparable numbers of both low- and high-affinity IL-2R. PMA/A23187-stimulated T cells from elderly subjects still proliferated less vigorously than did T cells from young persons. The addition of exogenous IL-2 to the cultured cells did not fully correct this age difference. Our findings that the expression of the IL-2, IL-2R, and IFN-gamma genes are not constitutionally defective in the elderly support the hypothesis that the age-related decline in proliferation observed in mitogen-stimulated T cells of the elderly is most likely attributable to alterations in the transmission of signals from the cell membrane to the nucleus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aging*
  • Calcimycin / pharmacology
  • Gene Expression Regulation / drug effects
  • Humans
  • Interferon-gamma / biosynthesis*
  • Interleukin-2 / physiology*
  • Lymphocyte Activation* / drug effects
  • RNA, Messenger / genetics
  • Receptors, Interleukin-2 / physiology*
  • T-Lymphocytes / physiology*
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Interleukin-2
  • RNA, Messenger
  • Receptors, Interleukin-2
  • Calcimycin
  • Interferon-gamma
  • Tetradecanoylphorbol Acetate