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Low Levels of Circulating CD4+FoxP3+ T Cells Are Associated With an Increased Risk for Development of Myocardial Infarction But Not for Stroke.

Wigren, Maria LU ; Björkbacka, Harry LU ; Andersson, Linda LU ; Ljungcrantz, Irena LU ; Nordin Fredrikson, Gunilla LU ; Persson, Margaretha LU ; Bryngelsson, Carl LU ; Hedblad, Bo LU and Nilsson, Jan LU (2012) In Arteriosclerosis, Thrombosis and Vascular Biology 32(8). p.2000-2007
Abstract
OBJECTIVE:

Regulatory T cells (Tregs) protect against atherosclerosis in experimental models, but their association with cardiovascular disease in humans remains to be elucidated. The aim of the present study was to determine whether circulating Tregs predict the development of acute cardiovascular events in humans.



METHODS AND RESULTS:

The study cohort consisted of a random sample of participants (n=700), aged 68 to 73 years, from the Malmo Diet and Cancer Study. Mononuclear leukocytes, stored at -140°C at the baseline investigation in 1991.1994, were thawed and Tregs, defined by the expression of FoxP3 in CD4+ T cells, were analyzed by flow cytometry. There was no detectable loss of cells during... (More)
OBJECTIVE:

Regulatory T cells (Tregs) protect against atherosclerosis in experimental models, but their association with cardiovascular disease in humans remains to be elucidated. The aim of the present study was to determine whether circulating Tregs predict the development of acute cardiovascular events in humans.



METHODS AND RESULTS:

The study cohort consisted of a random sample of participants (n=700), aged 68 to 73 years, from the Malmo Diet and Cancer Study. Mononuclear leukocytes, stored at -140°C at the baseline investigation in 1991.1994, were thawed and Tregs, defined by the expression of FoxP3 in CD4+ T cells, were analyzed by flow cytometry. There was no detectable loss of cells during storage, and the viability of thawed leukocytes was 95%. A low fraction of both CD4+FoxP3+ and CD4+CD25+FoxP3+ T cells was associated with a higher release of proinflammatory cytokines from activated mononuclear leukocytes, and this association was strongest for CD4+FoxP3+ cells. Eighty-four coronary events and 66 strokes were registered during follow-up until December 31, 2008. In a Cox proportional hazard regression model adjusting for major risk factors, low levels of baseline CD4+FoxP3+ T cells were associated with an increased risk for the development of acute coronary events but not stroke. There were no associations between CD4+CD25+FoxP3+ T cells and development of an acute coronary event or stroke.



CONCLUSIONS:

This study provides prospective evidence for the role of Tregs in the development of myocardial infarction. The findings are in accordance with previous experimental studies and provide clinical support for a protective role of Tregs in atherosclerosis. The lack of association between Tregs and stroke may reflect the more heterogeneous cause of this disease. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
immune system, coronary disease, lymphocytes, carotid arteries
in
Arteriosclerosis, Thrombosis and Vascular Biology
volume
32
issue
8
pages
2000 - 2007
publisher
American Heart Association
external identifiers
  • wos:000306558100040
  • pmid:22628434
  • scopus:84864282662
ISSN
1524-4636
DOI
10.1161/ATVBAHA.112.251579
language
English
LU publication?
yes
id
e1bafc31-ebfb-429c-a9e7-c79d065e7b71 (old id 2608489)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22628434?dopt=Abstract
date added to LUP
2012-06-04 20:46:48
date last changed
2017-11-05 03:19:54
@article{e1bafc31-ebfb-429c-a9e7-c79d065e7b71,
  abstract     = {OBJECTIVE: <br/><br>
Regulatory T cells (Tregs) protect against atherosclerosis in experimental models, but their association with cardiovascular disease in humans remains to be elucidated. The aim of the present study was to determine whether circulating Tregs predict the development of acute cardiovascular events in humans. <br/><br>
<br/><br>
METHODS AND RESULTS: <br/><br>
The study cohort consisted of a random sample of participants (n=700), aged 68 to 73 years, from the Malmo Diet and Cancer Study. Mononuclear leukocytes, stored at -140°C at the baseline investigation in 1991.1994, were thawed and Tregs, defined by the expression of FoxP3 in CD4+ T cells, were analyzed by flow cytometry. There was no detectable loss of cells during storage, and the viability of thawed leukocytes was 95%. A low fraction of both CD4+FoxP3+ and CD4+CD25+FoxP3+ T cells was associated with a higher release of proinflammatory cytokines from activated mononuclear leukocytes, and this association was strongest for CD4+FoxP3+ cells. Eighty-four coronary events and 66 strokes were registered during follow-up until December 31, 2008. In a Cox proportional hazard regression model adjusting for major risk factors, low levels of baseline CD4+FoxP3+ T cells were associated with an increased risk for the development of acute coronary events but not stroke. There were no associations between CD4+CD25+FoxP3+ T cells and development of an acute coronary event or stroke. <br/><br>
<br/><br>
CONCLUSIONS: <br/><br>
This study provides prospective evidence for the role of Tregs in the development of myocardial infarction. The findings are in accordance with previous experimental studies and provide clinical support for a protective role of Tregs in atherosclerosis. The lack of association between Tregs and stroke may reflect the more heterogeneous cause of this disease.},
  author       = {Wigren, Maria and Björkbacka, Harry and Andersson, Linda and Ljungcrantz, Irena and Nordin Fredrikson, Gunilla and Persson, Margaretha and Bryngelsson, Carl and Hedblad, Bo and Nilsson, Jan},
  issn         = {1524-4636},
  keyword      = {immune system,coronary disease,lymphocytes,carotid arteries},
  language     = {eng},
  number       = {8},
  pages        = {2000--2007},
  publisher    = {American Heart Association},
  series       = {Arteriosclerosis, Thrombosis and Vascular Biology},
  title        = {Low Levels of Circulating CD4+FoxP3+ T Cells Are Associated With an Increased Risk for Development of Myocardial Infarction But Not for Stroke.},
  url          = {http://dx.doi.org/10.1161/ATVBAHA.112.251579},
  volume       = {32},
  year         = {2012},
}