Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals.
OBJECTIVE
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
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.
School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.|Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
Jerrald L
JL
Rector
School of Health and Population Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
G Neil
GN
Thomas
School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.
Victoria E
VE
Burns
CUNY School of Public Health, New York, NY, USA.|CUNY Institute for Demographic Research, New York, NY, USA.
Jennifer B
JB
Dowd
Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
Raphael M
RM
Herr
Cancer Research UK Centre, University of Birmingham, Birmingham, UK.
Paul A
PA
Moss
Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
Marc N
MN
Jarczok
Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
Kristina
K
Hoffman
Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
Joachim E
JE
Fischer
Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany. j.a.bosch@uva.nl.|Department of Psychology, University of Amsterdam, Weesperplein 4, 1018 XA, Amsterdam, The Netherlands. j.a.bosch@uva.nl.
Jos A
JA
Bosch
D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000276:immunology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D000068884:Immunosenescence / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
CMV; Cholesterol; Cytomegalovirus; Diabetes; Glucose; Haemoglobin A1c; HbA1c; Immune ageing; Metabolic syndrome; T cell