Low numbers of FOXP3 positive regulatory T cells are present in all developmental stages of human atherosclerotic lesions.
BACKGROUND
T cell mediated inflammation contributes to atherogenesis and the onset of acute cardiovascular disease. Effector T cell functions are under a tight control of a specialized T cell subset, regulatory T cells (Treg). At present, nothing is known about the in situ presence of Treg in human atherosclerotic tissue. In the present study we investigated the frequency of naturally occurring Treg cells in all developmental stages of human atherosclerotic lesions including complicated thrombosed plaques.


METHODS
Normal arteries, early lesions (American Heart Association classification types I, II, and III), fibrosclerotic plaques (types Vb and Vc) and 'high risk' plaques (types IV, Va and VI) were obtained at surgery and autopsy. Serial sections were immunostained for markers specific for regulatory T cells (FOXP3 and GITR) and the frequency of these cells was expressed as a percentage of the total numbers of CD3+ T cells. Results were compared with Treg counts in biopsies of normal and inflammatory skin lesions (psoriasis, spongiotic dermatitis and lichen planus).


RESULTS
In normal vessel fragments T cells were virtually absent. Treg were present in the intima during all stages of plaque development (0.5-5%). Also in the adventitia of atherosclerotic vessels Treg were encountered, in similar low amounts. High risk lesions contained significantly increased numbers of Treg compared to early lesions (mean: 3.9 and 1.2%, respectively). The frequency of FOXP3+ cells in high risk lesions was also higher compared to stable lesions (1.7%), but this difference was not significant. The mean numbers of intimal FOXP3 positive cells in atherosclerotic lesions (2.4%) was much lower than those in normal (24.3%) or inflammatory skin lesions (28%).


CONCLUSIONS
Low frequencies of Treg in all developmental stages of human plaque formation could explain the smoldering chronic inflammatory process that takes place throughout the longstanding course of atherosclerosis.
de Boer
Onno J
OJ
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. o.j.deboer@amc.uva.nl
van der Meer
Jelger J
JJ
Teeling
Peter
P
van der Loos
Chris M
CM
van der Wal
Allard C
AC
D000818:Animals; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology; D017252:CD3 Complex / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology*; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D017475:Receptors, Nerve Growth Factor / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D012871:Skin Diseases / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053450:Glucocorticoid-Induced TNFR-Related Protein; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human
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