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NK-like T cells and plasma cytokines, but not anti-viral serology, define immune fingerprints of resilience and mild disability in exceptional aging.
Tuesday,2012-11-06 12:26 America/Los_Angeles — eenright
| Title | NK-like T cells and plasma cytokines, but not anti-viral serology, define immune fingerprints of resilience and mild disability in exceptional aging. |
| Publication Type | Journal Article |
| Year of Publication | 2011 |
| Authors | Vallejo, AN, Hamel, DL, Mueller, RG, Ives, DG, Michel, JJ, Boudreau, RM, Newman, AB |
| Journal | PLoS One |
| Volume | 6 |
| Issue | 10 |
| Pagination | e26558 |
| Date Published | 2011 |
| ISSN | 1932-6203 |
| Keywords | Adolescent, Adult, Aged, 80 and over, Aging, Cardiovascular Physiological Phenomena, CD56 Antigen, Cognition Disorders, Cytokines, Gene Expression Regulation, Humans, Immunity, Humoral, Killer Cells, Natural, Longevity, Male, NK Cell Lectin-Like Receptor Subfamily K, Phenotype, Physical Fitness, T-Lymphocyte Subsets, Young Adult |
| Abstract | <p>Exceptional aging has been defined as maintenance of physical and cognitive function beyond the median lifespan despite a history of diseases and/or concurrent subclinical conditions. Since immunity is vital to individual fitness, we examined immunologic fingerprint(s) of highly functional elders. Therefore, survivors of the Cardiovascular Health Study in Pittsburgh, Pennsylvania, USA were recruited (n = 140; mean age = 86 years) and underwent performance testing. Blood samples were collected and examined blindly for humoral factors and T cell phenotypes. Based on results of physical and cognitive performance testing, elders were classified as "impaired" or "unimpaired", accuracy of group assignment was verified by discriminant function analysis. The two groups showed distinct immune profiles as determined by factor analysis. The dominant immune signature of impaired elders consisted of interferon (IFN)-γ, interleukin (IL)-6, tumor necrosis factor-α, and T cells expressing inhibitory natural killer-related receptors (NKR) CD158a, CD158e, and NKG2A. In contrast, the dominant signature of unimpaired elders consisted of IL-5, IL-12p70, and IL-13 with co-expression of IFN-γ, IL-4, and IL-17, and T cells expressing stimulatory NKRs CD56, CD16, and NKG2D. In logistic regression models, unimpaired phenotype was predicted independently by IL-5 and by CD4(+)CD28(null)CD56(+)CD57(+) T cells. All elders had high antibody titers to common viruses including cytomegalovirus. In cellular bioassays, T cell receptor (TCR)-independent ligation of either CD56 or NKG2D elicited activation of T cells. Collectively, these data demonstrate the importance of immunological parameters in distinguishing between health phenotypes of older adults. NKR(+) T cells and cytokine upregulation indicate a unique physiologic environment in old age. Correlation of particular NKR(+) T cell subsets and IL-5 with unimpaired performance, and NKR-driven TCR-independent activation of T cells suggest novel immunopathway(s) that could be exploited to improve immunity in old age.</p> |
| DOI | 10.1371/journal.pone.0026558 |
| Alternate Journal | PLoS ONE |
| PubMed ID | 22028907 |
| PubMed Central ID | PMC3197651 |
| Grant List | R01 AG022379 / AG / NIA NIH HHS / United States P30 AG024827 / AG / NIA NIH HHS / United States UL1 TR000005 / TR / NCATS NIH HHS / United States R01 AG022379-06S1 / AG / NIA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01 HC075150 / HC / NHLBI NIH HHS / United States R01 AG030734 / AG / NIA NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States N01 HC085079 / HC / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 AG030734-02 / AG / NIA NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States T35 AG026778 / AG / NIA NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States |