Skewed representation of functionally distinct populations of Vgamma9Vdelta2 T lymphocytes in aging

Exp Gerontol. 2005 Jan-Feb;40(1-2):59-66. doi: 10.1016/j.exger.2004.09.008.

Abstract

We recently demonstrated that numerical and functional alterations of gammadelta T cells are present in healthy elderly. Here we observed that the decreased absolute number of Vgamma9Vdelta2 T cells present in old subjects in comparison with young/adult and middle aged donors is due to the reduction of naive and central memory Vgamma9Vdelta2 T cells bearing CD27 and CCR7 antigens. The proportion of effector/memory Vgamma9Vdelta2 T cells lacking CD27 or CCR7 markers was significantly increased in the peripheral blood of old subjects in comparison with younger donors. Moreover, the percentage of CD69+ gammadelta T cells was significantly increased in old subjects in comparison with younger donors after overnight activation, confirming that more effector cells are available in aged people. A functional analysis in young/adult and middle aged donors revealed that effector/memory CD27- Vgamma9Vdelta2 T cells are increased after 10-days of in vitro colture in the presence of isopentenylpyrophosphate (IPP) and IL-2. In contrast, the IPP+IL-2 mediated differentiation and expansion of CD27- effector/memory cells was absent in old subjects, confirming a lack of naive and central memory cells responding to IL-2. Accordingly, the expansion index of effector/memory CD27- Vgamma9Vdelta2 T cells was negatively correlated with the donor age. Finally, terminally differentiated Vgamma9Vdelta2 T cells measured as perforin content after 10-day in vitro expansion showed no age-related difference. These data demonstrated a shift of the circulating gammadelta T cell population towards CD27- and CCR7- effector T cells in the elderly with the reduction of immature CD27+ and CCR7+ T cell precursors.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / immunology*
  • Antigens, CD / blood
  • Antigens, Differentiation, T-Lymphocyte / blood
  • Cell Division / immunology
  • Cells, Cultured
  • Hemiterpenes / immunology
  • Humans
  • Interleukin-2 / immunology
  • Lectins, C-Type
  • Lymphocyte Activation / immunology
  • Lymphocyte Count
  • Middle Aged
  • Organophosphorus Compounds / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / blood*
  • Receptors, CCR7
  • Receptors, Chemokine / blood
  • T-Lymphocyte Subsets / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / blood

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CCR7 protein, human
  • CD69 antigen
  • Hemiterpenes
  • Interleukin-2
  • Lectins, C-Type
  • Organophosphorus Compounds
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, CCR7
  • Receptors, Chemokine
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • isopentenyl pyrophosphate