Accelerated development and aging of the immune system in p53-deficient mice

J Immunol. 1999 Aug 15;163(4):1966-72.

Abstract

Development and aging of the immune system lead to an accumulation of memory T cells over the long term. The predominance of T cells of the memory phenotype in the T cell population induces an age-related decline in protective immune responses. We found that development and aging of the immune system were accelerated in p53-deficient (p53-/-) mice; the accumulation of memory T cells was spontaneously accelerated, and a strong T cell-dependent Ab response and Th2 cytokine expression (IL-4, IL-6, and IL-10) were induced by Ag stimulation in young p53-/- mice in the developmental stage. The high T cell proliferative response in the young mice rapidly progressed to a depressed proliferative response in adult mice. It was suggested that the loss of regulation of the cell cycle, DNA repair, and apoptosis by p53 deficiency potentially leads to immunosenescence with the accumulation of memory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Aging / immunology*
  • Animals
  • Antibodies, Heterophile / biosynthesis
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cytokines / biosynthesis
  • Erythrocytes / immunology
  • Immune System / growth & development*
  • Immune System / immunology
  • Immunologic Memory / genetics
  • Lymphocyte Activation / genetics
  • Lymphoma / genetics
  • Lymphoma / immunology
  • Lymphoma / pathology
  • Male
  • Mice
  • Mice, Inbred CBA
  • Mice, Knockout
  • Receptors, Antigen, T-Cell / metabolism
  • Sheep
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / pathology
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / deficiency*
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Antibodies, Heterophile
  • Cytokines
  • Receptors, Antigen, T-Cell
  • Tumor Suppressor Protein p53