Distinctive immunoregulatory effects of adenosine on T cells of older humans

Charles S. Hesdorffer, Enkhzol Malchinkhuu, Arya Biragyn, Omar S. Mabrouk, Robert T. Kennedy, Karen Madara, Dennis D. Taub, Dan L. Longo, Janice B. Schwartz, Luigi Ferrucci, Edward J. Goetzl

Research output: Contribution to journalArticlepeer-review

Abstract

A role for adenosine in immunosenescence was investigated in T cells from older (≥65 yr) and younger (24-45 yr) healthy humans. Adenosine concentrations in cultures of activated T cells were significantly higher (P<0.0001) for older (145±47 nM, mean±SD) than younger (58±5.5 nM) subjects. Expression of the activation coreceptor CD28 was suppressed significantly by 0.1 to 1 μM exogenous adenosine, with greater effects of 1 μM (P<0.01) on T cells of younger (mean suppression of 67 and 65% for CD4 and CD8 T cells, respectively) than older (means of 42 and 46%) subjects. T-cell chemotaxis to CCL21 was suppressed significantly by 0.3 and 1 μM exogenous adenosine, with mean maximum decreases of 39 and 49%, respectively, for younger subjects and 28 and 31% for older subjects. Generation of IL-2 and IFN-γ by T cells of younger and older subjects was suppressed substantially only at adenosine levels of 3 μM or higher. Lower baseline expression of CD28 and chemotaxis to CCL21 and S1P for T cells from older subjects attributable to endogenous adenosine were reversed completely by two different A 2A adenosine receptor antagonists without affecting T cells of younger subjects. Adenosine is an endogenous T-cell immunosuppressor in older humans, and A 2A antagonists reverse adenosine-induced T-cell deficiencies of aging.

Original languageEnglish (US)
Pages (from-to)1301-1310
Number of pages10
JournalFASEB Journal
Volume26
Issue number3
DOIs
StatePublished - Mar 2012

Keywords

  • Cellular antigens
  • Chemotaxis
  • Cytokines
  • Immunodeficiency
  • Immunosenescence

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Distinctive immunoregulatory effects of adenosine on T cells of older humans'. Together they form a unique fingerprint.

Cite this