title: Distinctive immunoregulatory effects of adenosine on T cells of older humans.
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.
authors: National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
authors: Charles S
authors: CS
authors: Hesdorffer
authors: Enkhzol
authors: E
authors: Malchinkhuu
authors: Arya
authors: A
authors: Biragyn
authors: Omar S
authors: OS
authors: Mabrouk
authors: Robert T
authors: RT
authors: Kennedy
authors: Karen
authors: K
authors: Madara
authors: Dennis D
authors: DD
authors: Taub
authors: Dan L
authors: DL
authors: Longo
authors: Janice B
authors: JB
authors: Schwartz
authors: Luigi
authors: L
authors: Ferrucci
authors: Edward J
authors: EJ
authors: Goetzl
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001081:Apyrase / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D010627:Phenethylamines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology; D055815:Young Adult
chemical_list: C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D015703:Antigens, CD; D018106:CD28 Antigens; D016207:Cytokines; D010627:Phenethylamines; D011743:Pyrimidines; D014230:Triazoles; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C010192:9-(2-hydroxy-3-nonyl)adenine; D001081:Apyrase; C067869:CD39 antigen; D000225:Adenine; D000241:Adenosine