Impaired in vivo CD4+ T cell expansion and differentiation in aged mice is not solely due to T cell defects: decreased stimulation by aged dendritic cells

Mech Ageing Dev. 2011 Apr;132(4):187-94. doi: 10.1016/j.mad.2011.03.005. Epub 2011 Mar 29.


CD4+ T cells regulate humoral and cell-mediated immune responses, which are progressively impaired in aging, resulting in susceptibility to infections and cancer. Dendritic cells (DCs) are major activators of T cells, providing signals that drive their expansion and differentiation. In this study, we asked if decreased CD4+ T cell responses were influenced by the age of DCs rather than being exclusively due to T cell defects. Old T cells transferred to young recipients expanded and differentiated similarly to young T cells. However, aged recipients were poor stimulators of both old and young T cells, which failed to acquire CD44 expression and produce interferon gamma (IFN-γ). DCs in aged hosts expressed fewer MHC-peptide complexes. The CD86 expression in the DCs of both hosts was similar; however, CD40 levels were reduced in old DCs. Finally, old DCs failed to produce inflammatory cytokines in response to LPS. Our results indicate that the impairment of aged CD4+ T cell function is intimately related to multiple alterations in aged DCs, rather than being caused solely by intrinsic T cell defects, suggesting that the function of aged T cells may be partially rescued in vivo when appropriate stimulation is applied. These findings are relevant to vaccination design for elderly populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging
  • Animals
  • Antigen Presentation
  • CD4-Positive T-Lymphocytes / cytology*
  • CD40 Antigens / biosynthesis
  • Cell Differentiation
  • Cytokines / metabolism
  • Dendritic Cells / cytology*
  • Hyaluronan Receptors / biosynthesis
  • Interferon-gamma / metabolism
  • Lipopolysaccharides / metabolism
  • Major Histocompatibility Complex
  • Mice
  • Mice, Inbred C57BL
  • Peptides / chemistry


  • CD40 Antigens
  • Cytokines
  • Hyaluronan Receptors
  • Lipopolysaccharides
  • Peptides
  • Interferon-gamma