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Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals
AIMS/HYPOTHESIS: Biological ageing of the immune system, or immunosenescence, predicts poor health and increased mortality. A hallmark of immunosenescence is the accumulation of differentiated cytotoxic T cells (CD27(−)CD45RA(+/−); or dCTLs), partially driven by infection with the cytomegalovirus (C...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589544/ https://www.ncbi.nlm.nih.gov/pubmed/26290049 http://dx.doi.org/10.1007/s00125-015-3731-4 |
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author | Rector, Jerrald L. Thomas, G. Neil Burns, Victoria E. Dowd, Jennifer B. Herr, Raphael M. Moss, Paul A. Jarczok, Marc N. Hoffman, Kristina Fischer, Joachim E. Bosch, Jos A. |
author_facet | Rector, Jerrald L. Thomas, G. Neil Burns, Victoria E. Dowd, Jennifer B. Herr, Raphael M. Moss, Paul A. Jarczok, Marc N. Hoffman, Kristina Fischer, Joachim E. Bosch, Jos A. |
author_sort | Rector, Jerrald L. |
collection | PubMed |
description | AIMS/HYPOTHESIS: Biological ageing of the immune system, or immunosenescence, predicts poor health and increased mortality. A hallmark of immunosenescence is the accumulation of differentiated cytotoxic T cells (CD27(−)CD45RA(+/−); or dCTLs), partially driven by infection with the cytomegalovirus (CMV). Immune impairments reminiscent of immunosenescence are also observed in hyperglycaemia, and in vitro studies have illustrated mechanisms by which elevated glucose can lead to increased dCTLs. This study explored associations between glucose dysregulation and markers of immunosenescence in CMV(+) and CMV(−) individuals. METHODS: A cross-sectional sample of participants from an occupational cohort study (n = 1,103, mean age 40 years, 88% male) were assessed for HbA(1c) and fasting glucose levels, diabetes, cardiovascular risk factors (e.g. lipids), numbers of circulating effector memory (EM; CD27(−)CD45RA(−)) and CD45RA re-expressing effector memory (EMRA; CD27(−)CD45RA(+)) T cells, and CMV infection status. Self-report and physical examination assessed anthropometric, sociodemographic and lifestyle factors. RESULTS: Among CMV(+) individuals (n = 400), elevated HbA(1c) was associated with increased numbers of EM (B = 2.75, p < 0.01) and EMRA (B = 2.90, p < 0.01) T cells, which was robust to adjustment for age, sex, sociodemographic variables and lifestyle factors. Elevated EM T cells were also positively associated with total cholesterol (B = 0.04, p < 0.05) after applying similar adjustments. No associations were observed in CMV(−) individuals. CONCLUSIONS/INTERPRETATION: The present study identified consistent associations of unfavourable glucose and lipid profiles with accumulation of dCTLs in CMV(+) individuals. These results provide evidence that the impact of metabolic risk factors on immunity and health can be co-determined by infectious factors, and provide a novel pathway linking metabolic risk factors with accelerated immunosenescence. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-015-3731-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users. |
format | Online Article Text |
id | pubmed-4589544 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-45895442015-10-06 Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals Rector, Jerrald L. Thomas, G. Neil Burns, Victoria E. Dowd, Jennifer B. Herr, Raphael M. Moss, Paul A. Jarczok, Marc N. Hoffman, Kristina Fischer, Joachim E. Bosch, Jos A. Diabetologia Article AIMS/HYPOTHESIS: Biological ageing of the immune system, or immunosenescence, predicts poor health and increased mortality. A hallmark of immunosenescence is the accumulation of differentiated cytotoxic T cells (CD27(−)CD45RA(+/−); or dCTLs), partially driven by infection with the cytomegalovirus (CMV). Immune impairments reminiscent of immunosenescence are also observed in hyperglycaemia, and in vitro studies have illustrated mechanisms by which elevated glucose can lead to increased dCTLs. This study explored associations between glucose dysregulation and markers of immunosenescence in CMV(+) and CMV(−) individuals. METHODS: A cross-sectional sample of participants from an occupational cohort study (n = 1,103, mean age 40 years, 88% male) were assessed for HbA(1c) and fasting glucose levels, diabetes, cardiovascular risk factors (e.g. lipids), numbers of circulating effector memory (EM; CD27(−)CD45RA(−)) and CD45RA re-expressing effector memory (EMRA; CD27(−)CD45RA(+)) T cells, and CMV infection status. Self-report and physical examination assessed anthropometric, sociodemographic and lifestyle factors. RESULTS: Among CMV(+) individuals (n = 400), elevated HbA(1c) was associated with increased numbers of EM (B = 2.75, p < 0.01) and EMRA (B = 2.90, p < 0.01) T cells, which was robust to adjustment for age, sex, sociodemographic variables and lifestyle factors. Elevated EM T cells were also positively associated with total cholesterol (B = 0.04, p < 0.05) after applying similar adjustments. No associations were observed in CMV(−) individuals. CONCLUSIONS/INTERPRETATION: The present study identified consistent associations of unfavourable glucose and lipid profiles with accumulation of dCTLs in CMV(+) individuals. These results provide evidence that the impact of metabolic risk factors on immunity and health can be co-determined by infectious factors, and provide a novel pathway linking metabolic risk factors with accelerated immunosenescence. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-015-3731-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users. Springer Berlin Heidelberg 2015-08-20 2015 /pmc/articles/PMC4589544/ /pubmed/26290049 http://dx.doi.org/10.1007/s00125-015-3731-4 Text en © The Author(s) 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Article Rector, Jerrald L. Thomas, G. Neil Burns, Victoria E. Dowd, Jennifer B. Herr, Raphael M. Moss, Paul A. Jarczok, Marc N. Hoffman, Kristina Fischer, Joachim E. Bosch, Jos A. Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals |
title | Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals |
title_full | Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals |
title_fullStr | Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals |
title_full_unstemmed | Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals |
title_short | Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals |
title_sort | elevated hba(1c) levels and the accumulation of differentiated t cells in cmv(+) individuals |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589544/ https://www.ncbi.nlm.nih.gov/pubmed/26290049 http://dx.doi.org/10.1007/s00125-015-3731-4 |
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