The impact of aging on memory T cell phenotype and function in the human bone marrow

J Leukoc Biol. 2012 Feb;91(2):197-205. doi: 10.1189/jlb.0611299. Epub 2011 Oct 19.

Abstract

Recently, the BM has been shown to play a key role in regulating the survival and function of memory T cells. However, the impact of aging on these processes has not yet been studied. We demonstrate that the number of CD4⁺ and CD8⁺ T cells in the BM is maintained during aging. However, the composition of the T cell pool in the aged BM is altered with a decline of naïve and an increase in T(EM) cells. In contrast to the PB, a highly activated CD8⁺CD28⁻ T cell population, which lacks the late differentiation marker CD57, accumulates in the BM of elderly persons. IL-6 and IL-15, which are both increased in the aged BM, efficiently induce the activation, proliferation, and differentiation of CD8⁺ T cells in vitro, highlighting a role of these cytokines in the age-dependent accumulation of highly activated CD8⁺CD28⁻ T cells in the BM. Yet, these age-related changes do not impair the maintenance of a high number of polyfunctional memory CD4⁺ and CD8⁺ T cells in the BM of elderly persons. In summary, aging leads to the accumulation of a highly activated CD8⁺CD28⁻ T cell population in the BM, which is driven by the age-related increase of IL-6 and IL-15. Despite these changes, the aged BM is a rich source of polyfunctional memory T cells and may thus represent an important line of defense to fight recurrent infections in old age.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aging / immunology*
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Bone Marrow / immunology*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Cells, Cultured / drug effects
  • Cells, Cultured / immunology
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Female
  • Gene Rearrangement, T-Lymphocyte
  • Humans
  • Immunologic Memory*
  • Ionomycin / pharmacology
  • Lymphocyte Count
  • Male
  • Middle Aged
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • Cytokines
  • Ionomycin
  • Tetradecanoylphorbol Acetate