Plaque-infiltrating T lymphocytes in patients with carotid atherosclerosis: an insight into the cellular mechanisms associated to plaque destabilization.
OBJECTIVE
Inflammation plays a crucial role in the progression of atherosclerotic plaques. The aim of the present study was to investigate phenotypic and functional characteristics of plaque-infiltrating T lymphocytes associated with a complicated phenotype of carotid atherosclerotic lesions.


METHODS
Atherosclerotic plaques were obtained from 17 patients undergoing carotid endarterectomy and cultured to isolate infiltrating T lymphocytes. Blood samples were obtained from patients and from 20 sex- and age-matched healthy subjects. The presence of lymphocytes (CD3+ cells) within atherosclerotic plaques was determined by immunohistochemistry. Phenotypic characteristics and intracellular cytokine expression of plaque-infiltrating and circulating T lymphocytes were determined by flow cytometry. Cytokine levels in supernatants from infiltrating T cell cultures were evaluated by enzyme-linked immunosorbent assay.


RESULTS
A higher number of CD3+ cells was detected in complicated than in uncomplicated plaques. Complicated plaques had higher percentages of tumor necrosis factor (TNF)-α- and interferon (IFN)-γ- positive cells than uncomplicated ones, especially in CD4+ subpopulation. In patients the percentages of TNF-α-positive cells were higher in infiltrating than in circulating lymphocyte samples. Intracellular TNF-α, IFN-γ, interleukin (IL)-4 and IL-10 expression resulted higher in circulating lymphocyte samples from patients than in those from healthy subjects. Supernatants of infiltrating T cell cultures from complicated plaques showed higher levels of TNF-α and lower levels of IL-4 than those from uncomplicated plaques.


CONCLUSIONS
Our data provide new information on the presence of increased percentages of pro-inflammatory T lymphocytes in complicated plaques with respect to uncomplicated ones and support the concept of the key role played by activated T cells in the progression of atherosclerotic lesions.
Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
E
E
Profumo
B
B
Buttari
M E
ME
Tosti
A
A
Tagliani
R
R
Capoano
G
G
D'Amati
R
R
Businaro
B
B
Salvati
R
R
Riganò
D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000276:immunology; D002340:Carotid Artery Diseases / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D016207:Cytokines / Q000378:metabolism; D016894:Endarterectomy, Carotid; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D017252:CD3 Complex; D016207:Cytokines