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 language | English (US) |
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Pages (from-to) | 1301-1310 |
Number of pages | 10 |
Journal | FASEB Journal |
Volume | 26 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2012 |
Externally published | Yes |
Keywords
- Cellular antigens
- Chemotaxis
- Cytokines
- Immunodeficiency
- Immunosenescence
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics