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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

Vallejo, AN and Hamel, DL and Mueller, RG and Ives, DG and Michel, JJ and Boudreau, RM and Newman, AB (2011) Nk-like T cells and plasma cytokines, but Not Anti-Viral serology, define immune fingerprints of resilience and mild disability in exceptional aging. PLoS ONE, 6 (10).

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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 nullCD56 +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. © 2011 Vallejo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Vallejo, AN
Hamel, DL
Mueller, RG
Ives, DGIvesD@edc.pitt.eduDIANIVES
Michel, JJjjm80@pitt.eduJJM80
Boudreau, RMrob21@pitt.eduROB21
ContributionContributors NameEmailPitt UsernameORCID
Centers: Other Centers, Institutes, Offices, or Units > McGowan Institute for Regenerative Medicine
Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 25 October 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 10
DOI or Unique Handle: 10.1371/journal.pone.0026558
Schools and Programs: School of Public Health > Epidemiology
School of Medicine > Immunology
School of Medicine > Pediatrics
Refereed: Yes
MeSH Headings: Adolescent; Adult; Aged, 80 and over; Aging--blood; Aging--immunology; Aging--physiology; Antigens, CD56--metabolism; Cardiovascular Physiological Processes; Cognition Disorders--blood; Cognition Disorders--immunology; Cognition Disorders--physiopathology; Cytokines--blood; Gene Expression Regulation--immunology; Humans; Immunity, Humoral; Killer Cells, Natural--immunology; Longevity--immunology; Longevity--physiology; Male; NK Cell Lectin-Like Receptor Subfamily K--metabolism; Phenotype; Physical Fitness--physiology; T-Lymphocyte Subsets--immunology; T-Lymphocyte Subsets--metabolism; Young Adult
Other ID: NLM PMC3197651
PubMed Central ID: PMC3197651
PubMed ID: 22028907
Date Deposited: 07 Sep 2012 20:46
Last Modified: 02 Jul 2022 10:57


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