title: Detection of TCD4+ subsets in human carotid atheroma.
abstract: Activated TCD4(+) cells are detected in human atherosclerotic plaques which indicate their participation in disease progression and destabilization. Among these cells, IFN-γ-producing T cells (TH1) are recognized as having a pro-atherogenic role. Recently, the IL-17-producing T helper lineage of cells (TH17) has been identified in atherosclerotic lesions. They have been linked to atheroma development through the production of pro-inflammatory mediators present in these lesions. Furthermore, IL-22 producing TCD4(+) cells (TH22) have been identified in the atheromatous environment, but their presence and function has not been investigated. The aim of this study was to analyze the immune response mediated by pro-inflammatory subtypes of TCD4(+) cells in atheromatous lesions. Atherosclerotic plaques of 57 patients with critical stenosis of carotid submitted to endarterectomy were evaluated. Three carotid fragments from organ donors were used as control. mRNA analysis showed expression of TH1 (IFN-γ, T-bet, IL-2, IL-12p35, TNF-α and IL-18); TH2 (GATA-3); TH17 (IL-17A, IL-17RA, Rorγt, TGF-β, IL-6, IL-1β, IL-23p19, CCL20, CCR4 and CCR6) and TH22 (IL-22 and Ahr) related markers. Asymptomatic patients showed higher expression of mRNA of IL-10, TGF-β, CCR4 and GATA-3 when compared to symptomatic ones. Immunohistochemistry analysis showed higher levels of IL-23, TGF-β, IL-1β and IL-18 in macrophages and foam cells in unstable lesions compared to stable and control ones. In vitro stimulation of atheroma cells induced IL-17 and IFN-γ production. Finally we were able to detect, the following subpopulations of TCD3(+) cells: TCD4(+) IFN-γ(+), TCD4(+)IL-17(+), TCD4(+)IL-4(+), TCD4(+)IL-22(+) and double positive cells (IFN-γ/IL-17(+), IFN-γ/IL-22(+) or IL-17/IL-22(+)). Our results showed the presence of distinct TCD4(+) cells subsets in human carotid lesions and suggest that interactions among them may contribute to the atheroma progression and destabilization.
authors.affiliation: Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
authors.forename: Rômulo Tadeu Dias
authors.initials: RT
authors.lastname: Oliveira
authors.forename: Rosiane Maria
authors.initials: RM
authors.lastname: Silva
authors.forename: Fabio Haach
authors.initials: FH
authors.lastname: Teo
authors.forename: Marcela Franco
authors.initials: MF
authors.lastname: Mineiro
authors.forename: Maria Carolina
authors.initials: MC
authors.lastname: Ferreira
authors.forename: Albina
authors.initials: A
authors.lastname: Altemani
authors.forename: Ronei Luciano
authors.initials: RL
authors.lastname: Mamoni
authors.forename: Fábio Husseman
authors.initials: FH
authors.lastname: Menezes
authors.forename: Maria Heloisa Souza Lima
authors.initials: MH
authors.lastname: Blotta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002339:Carotid Arteries / Q000276:immunology* / Q000473:pathology* / Q000601:surgery; D004691:Endarterectomy; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054398:Receptors, CCR4 / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: C515354:CCR4 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D012333:RNA, Messenger; D054398:Receptors, CCR4; D016212:Transforming Growth Factor beta; D016753:Interleukin-10