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Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals.

Rector JL, Thomas GN, Burns VE, Dowd JB, Herr RM, Moss PA, Jarczok MN, Hoffman K, Fischer JE, Bosch JA - Diabetologia (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Unadjusted comparison of (a) EM (CD27−CD45RA−) and (b) EMRA (CD27−CD45RA+) CD8+ T cell subset numbers by glycaemic status and CMV infection. White bars, normoglycaemic; black bars, hyperglycaemic. *p < 0.05 and ***p < 0.001 represent levels of significant difference from normoglycaemic. †p < 0.001 represents significant difference from CMV−
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Fig1: Unadjusted comparison of (a) EM (CD27−CD45RA−) and (b) EMRA (CD27−CD45RA+) CD8+ T cell subset numbers by glycaemic status and CMV infection. White bars, normoglycaemic; black bars, hyperglycaemic. *p < 0.05 and ***p < 0.001 represent levels of significant difference from normoglycaemic. †p < 0.001 represents significant difference from CMV−

Mentions: Fig. 1 shows the unadjusted comparisons of EM and EMRA T cell numbers stratified by glycaemic status and CMV infection. For all participants, individuals classified as hyperglycaemic had 26.6% higher numbers of EM (110.2 vs 87.0 cells/μl) and 41.2% higher EMRA T cells (218.1 vs 154.5 cells/μl; both p < 0.001) than normoglycaemic participants.Fig. 1


Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals.

Rector JL, Thomas GN, Burns VE, Dowd JB, Herr RM, Moss PA, Jarczok MN, Hoffman K, Fischer JE, Bosch JA - Diabetologia (2015)

Unadjusted comparison of (a) EM (CD27−CD45RA−) and (b) EMRA (CD27−CD45RA+) CD8+ T cell subset numbers by glycaemic status and CMV infection. White bars, normoglycaemic; black bars, hyperglycaemic. *p < 0.05 and ***p < 0.001 represent levels of significant difference from normoglycaemic. †p < 0.001 represents significant difference from CMV−
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4589544&req=5

Fig1: Unadjusted comparison of (a) EM (CD27−CD45RA−) and (b) EMRA (CD27−CD45RA+) CD8+ T cell subset numbers by glycaemic status and CMV infection. White bars, normoglycaemic; black bars, hyperglycaemic. *p < 0.05 and ***p < 0.001 represent levels of significant difference from normoglycaemic. †p < 0.001 represents significant difference from CMV−
Mentions: Fig. 1 shows the unadjusted comparisons of EM and EMRA T cell numbers stratified by glycaemic status and CMV infection. For all participants, individuals classified as hyperglycaemic had 26.6% higher numbers of EM (110.2 vs 87.0 cells/μl) and 41.2% higher EMRA T cells (218.1 vs 154.5 cells/μl; both p < 0.001) than normoglycaemic participants.Fig. 1

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus