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Altered Metabolism and Function of T Cells Isolated from Influenza Vaccinated Obese Adults
Author(s) -
Green William David,
Rebeles Jennifer,
Noah Terry J,
Hudgens Michael G,
Weir Sam S,
MacIver Nancie J,
Beck Melinda A
Publication year - 2017
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/fasebj.31.1_supplement.434.3
Subject(s) - medicine , immunology , obesity , vaccination , cd8 , virus , influenza vaccine , immune system
In 2009, obesity was identified as an independent risk factor for increased morbidity and mortality to infection with influenza. Currently, vaccination provides the best protection against influenza infection. Given the high prevalence of obesity within the United States, coupled with the associated risk of obesity and influenza‐related poor health outcomes, our laboratory studies the effects of obesity on the influenza vaccine response. Previously, we demonstrated that, compared with vaccinated healthy weight adults, influenza‐specific CD4+ and CD8+ T cells from vaccinated obese adults were less activated and expressed fewer functional markers. We hypothesized that the mechanism responsible for the impaired vaccine response was due to obesity‐induced alterations in the metabolic profile of these T cells. To elucidate the influence of obesity as an independent metabolic factor, we recruited 30 women, ages 35–65, who were either healthy weight (18.5 < BMI < 24.9) or obese (BMI ≥ 30.0) with no history of autoimmune disease or conditions that would be immunosuppressive. Metabolic profiles of cells were determined using the Agilent XFe96 Flux Analyzer immediately following isolation and at 72‐hours post CD3/CD28 activation. Additionally, freshly isolated PBMCs were cultured with a strain of influenza virus represented in the vaccine all subjects received, A/California/7/2009 (H1N1) virus, for 72 hours. Following stimulation, the cells were stained for intracellular and extracellular functional markers and analyzed on the BD LSRII flow cytometer. We found that freshly isolated (quiescent) CD4 + and CD8 + T cells showed no metabolic differences among groups. However, upon stimulation, CD4 + and CD8 + T cells from obese subjects showed higher basal respiration and basal glycolytic rates compared to cells from healthy weight subjects. Furthermore, obese cells showed reduced spare‐respiratory capacity compared to healthy weight. Correlating with the differences in metabolism, activation and functional markers were lower on cells from obese subjects. These results suggest that metabolic and hormonal dysregulation associated with obesity alters the cellular metabolism of influenza‐specific T cells. This alteration in metabolism likely impairs their ability to respond to influenza, thereby resulting in higher influenza morbidity and mortality in an obese population. Our findings suggest that obesity‐driven metabolic changes in immune cells may impair the response to other vaccines as well, putting an increasingly obese population at higher risk for vaccine failures. Support or Funding Information NIH Grant RO1 AI078090, P30DK056350 IRB 08‐1606