The Ratio of Regulatory (FOXP3+) to Total (CD3+) T Cells Determined by Epigenetic Cell Counting and Cardiovascular Disease Risk: A Prospective Case-cohort Study in Non-diabetics
| Autor: | Sven Olek, Theron Johnson, Tilman Kühn, Rudolf Kaaks, Sebastian Dietmar Barth, Janika Josephin Schulze, Verena Katzke, Katharina Gellhaus |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Oncology CD3 Complex Foxp3 + regulatory T cells (Tregs) lcsh:Medicine 030204 cardiovascular system & hematology T-Lymphocytes Regulatory Foxp3+ regulatory T cells (Tregs) Epigenesis Genetic Immune tolerance Cell-type-specific epigenetic qPCR-assays 0302 clinical medicine T-Lymphocyte Subsets Prospective cohort study lcsh:R5-920 education.field_of_study Incidence Hazard ratio FOXP3 Forkhead Transcription Factors General Medicine Middle Aged European Prospective Investigation into Cancer and Nutrition Phenotype medicine.anatomical_structure Cardiovascular Diseases Population Surveillance Female lcsh:Medicine (General) Research Paper Adult Risk medicine.medical_specialty Regulatory T cell Population Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Internal medicine medicine Humans Lymphocyte Count Prospective study education Aged Proportional Hazards Models lcsh:R Case-control study Cardiovascular disease risk 030104 developmental biology Case-Control Studies Immunology Follow-Up Studies |
| Zdroj: | Barth, S D, Kaaks, R, Johnson, T, Katzke, V, Gellhaus, K, Schulze, J J, Olek, S & Kuhn, T 2016, ' The Ratio of Regulatory (FOXP3+) to Total (CD3+) T Cells Determined by Epigenetic Cell Counting and Cardiovascular Disease Risk: A Prospective Case-cohort Study in Non-diabetics ', EBioMedicine, vol. 11, pp. 151-156 . https://doi.org/10.1016/j.ebiom.2016.07.035 EBioMedicine EBioMedicine, Vol 11, Iss C, Pp 151-156 (2016) |
| DOI: | 10.1016/j.ebiom.2016.07.035 |
| Popis: | Background Experimental and clinical evidence indicate that inflammatory processes in atherogenesis and the development of cardiovascular complications are promoted by a loss of regulatory T cell (Treg)-mediated immunological tolerance to plaque antigens. Yet, the association between alterations of systemic Treg frequency and cardiovascular disease incidence remains uncertain. Methods A nested case-cohort study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg, comprising a random subcohort (n = 778) and primary cases of myocardial infarction (MI, n = 276) and ischemic stroke (n = 151). Pre-diagnostic FOXP3 + Treg and total CD3 + T-lymphocyte (tTL) frequencies in blood were measured by epigenetic-based, quantitative real-time PCR-assisted cell counting. Results Multivariate, Prentice-weighted Cox regression analyses revealed that lower Treg/tTL ratios were not associated with the risk of either MI (lowest vs. highest sex-specific quartile; hazard ratio: 0.72, 95% confidence interval: 0.46 to 1.13; Ptrend = 0.51) or stroke (HR: 0.90, 95% CI: 0.51 to 1.60; Ptrend = 0.78). There were no correlations of Treg/tTL ratios with C-reactive protein, HbA1c, and various lipid parameters. Conclusions Among middle-aged adults from the general population, imbalances in the relative frequency of Tregs within the total T cell compartment do not confer an increased risk of MI or stroke. Highlights • We studied if peripheral immune tolerance, as reflected by regulatory (FOXP3+) to total (CD3+) T cells, relates to CVD risk. • Epigenetic-based, qPCR assisted cell counting was used to quantify T cell subsets in long-term stored buffy coat samples. • Lower Treg-mediated immune tolerance does not confer an increased risk of major CVD events. Inflammation in the arterial intima plays a central role in atherosclerotic cardiovascular disease and may develop owing to autoimmune-like responses targeted against plaque antigens. While the ratio between regulatory T cells (Tregs) and effector T cells is thought to control such immune response outcomes and tolerance within the T cell compartment, we found no association with incidence of major CVD events. These findings imply that reduced systemic Treg frequencies observed in CVD patients follow rather than precede disease manifestation and that Treg variation within a physiological range may not – as previously reported - constitute a pre-disposing risk factor for CVD. |
| Databáze: | OpenAIRE |
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