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Distinctive immunoregulatory effects of adenosine on T cells of older humans
Author(s) -
Hesdorffer Charles S.,
Malchinkhuu Enkhzol,
Biragyn Arya,
Mabrouk Omar S.,
Kennedy Robert T.,
Madara Karen,
Taub Dennis D.,
Longo Dan L.,
Schwartz Janice B.,
Ferrucci Luigi,
Goetzl Edward J.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.11-197046
Subject(s) - adenosine , immunosenescence , cd28 , adenosine receptor , medicine , endocrinology , cd8 , endogeny , adenosine kinase , t cell , chemotaxis , immunology , chemistry , receptor , biology , immune system , adenosine deaminase , agonist
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.—Hesdorffer, H. S., Malchinkhuu, E., Biragyn, A., Mabrouk, O. S., Kennedy, R. T., Madara, K., Taub, D. D., Longo, D. L., Schwartz, J. B., Ferrucci, L., Goetzl, E. J. Distinctive immunoregulatory effects of adenosine on T cells of older humans. FASEB J. 26, 1301‐1310 (2012). www.fasebj.org