Impaired Antigen-Induced CD8+ T Cell Clonal Expansion in Aging Is Due to Defects in Antigen Presenting Cell Function

Cell Immunol. 2004 Jun;229(2):86-92. doi: 10.1016/j.cellimm.2004.07.001.

Abstract

CD8+ T cell activation depends on interaction with antigen-presenting cells (APCs) and this interaction leads to the expansion of T cells with the capacity to control infection. Using professional APCs, we demonstrate that with age, the duration of APC-T cell contact time required to achieve clonal expansion increases. Naïve CD8+ T cells from aged mice showed no defect in antigen-induced proliferation when stimulated with APC from young mice. In contrast, CD8+ T cells from young mice exhibited reduced clonal expansion and secreted significantly lower amounts of IFN-gamma when stimulated by APCs from aged mice. The aged APCs were defective in costimulatory molecule expression and cytokine and chemokine secretion. These data indicate that defects in APC function lead to poor T cell clonal expansion and function in aging.

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigen-Presenting Cells / cytology
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Communication / immunology
  • Cellular Senescence / immunology
  • Clone Cells / cytology
  • Clone Cells / immunology
  • CpG Islands / immunology
  • Cytokines / immunology
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Interferon-gamma / immunology
  • L-Selectin / immunology
  • Lymphocyte Activation / immunology
  • Macrophages, Peritoneal / cytology
  • Macrophages, Peritoneal / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / immunology
  • Thioglycolates / pharmacology

Substances

  • Cytokines
  • Receptors, Antigen, T-Cell
  • Thioglycolates
  • L-Selectin
  • Interferon-gamma