Impairment of CD3-dependent and CD3-independent Activation Pathways in CD4+ and in CD8+ T Cells From Old CBA/RIJ Mice

Mech Ageing Dev. 1990 Apr 9;53(2):141-55. doi: 10.1016/0047-6374(90)90066-o.

Abstract

Stimulation of T cells from old mice with anti-CD3 antibodies resulted in a high variability of proliferative responses, which were 2- to 8-fold lower than the responses by T cells from young mice, even in the presence of exogenous rIL-2. Moreover, the CD4+ T cells from these old mice displayed a diminished capacity to produce IL-2 in response to anti-CD3. A partial explanation was found in the observation that T cells from the majority of old mice displayed a diminished expression of CD3 of variable intensity. However, after stimulation of the T cells with the combination of phorbol-12-myristate-13-acetate (PMA) and ionomycin to bypass CD3, 3 out of 6 old mice still exhibited 2-fold lower proliferative responses than T cells from young mice; IL-2 production by the CD4+ T cells was lower in all old mice tested. Comparison of CD4+ T cells and CD8+ T cells from old mice revealed a defective PMA/ionomycin response in both subsets, although this defect seemed more pronounced in CD4+ T cells when compared with the young counterparts. The diminished response of CD8+ T cells was accompanied by a diminished expression of the IL-2R alpha-chain. In contrast, old CD4+ T cells expressed rather higher levels of IL-2R alpha-chain than young CD4+ T cells. Altogether, multiple defects which are not necessarily the same in CD4+ and CD8+ T cells are responsible for defective T cell responses in old mice.

MeSH terms

  • Aging / immunology*
  • Animals
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • CD4-Positive T-Lymphocytes / immunology
  • CD8 Antigens
  • In Vitro Techniques
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / pharmacology
  • Ionomycin / pharmacology
  • Lymphocyte Activation* / drug effects
  • Male
  • Mice
  • Mice, Inbred CBA
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2 / biosynthesis
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • CD8 Antigens
  • Interleukin-2
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Ionomycin
  • Tetradecanoylphorbol Acetate