title: Characterization of CD4+CD28null T cells in patients with coronary artery disease and individuals with risk factors for atherosclerosis.
abstract: Risk factors for atherosclerosis may contribute to chronic low-grade inflammation. A highly cytotoxic and inflammatory CD4(+) cell subset (CD4(+)CD28(null) cells) has been associated with inflammatory diseases, including acute coronary syndromes (ACS). The aim of this study was to quantify and characterize CD4(+)CD28(null) cells in individuals with risk factors for atherosclerosis and patients with coronary artery disease (CAD). In order to achieve this goal, peripheral blood mononuclear cells (PBMCs) from individuals with risk factors for atherosclerosis and patients with CAD were analyzed using flow cytometry to detect cytotoxic molecules and evaluate the expression of homing receptors and inflammatory cytokines in CD4(+) cell subsets. The cells were evaluated ex vivo and after stimulation in culture. We found no differences in the proportions of CD4(+)CD28(null) cells among the groups. Compared with the CD4(+)CD28(+) population, the ex vivo CD4(+)CD28(null) subset from all groups expressed higher levels of granzymes A and B, perforin, granulysin and interferon-γ (IFN-γ). Individuals with risk factors and patients with ACS showed the highest levels of cytotoxic molecules. After stimulation, tumor necrosis factor-α (TNF-α) expression in the CD4(+)CD28(null) subset from these groups increased more than in the other groups. Stimulation with LPS decreased the expression of cytotoxic molecules by CD4(+)CD28(null) cells in all groups. In conclusion, our results show that risk factors for atherosclerosis may alter the CD4(+)CD28(null) cells phenotype, increasing their cytotoxic potential. Our findings also suggest that CD4(+)CD28(null) cells may participate in the early phases of atherosclerosis.
authors: Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
authors: Fábio Haach
authors: FH
authors: Téo
authors: Rômulo Tadeu Dias
authors: RT
authors: de Oliveira
authors: Ronei Luciano
authors: RL
authors: Mamoni
authors: Maria Carolina Salmora
authors: MC
authors: Ferreira
authors: Wilson
authors: W
authors: Nadruz
authors: Otávio Rizzi
authors: OR
authors: Coelho
authors: Juliano de Lara
authors: Jde L
authors: Fernandes
authors: Maria Heloisa Souza Lima
authors: MH
authors: Blotta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D050197:Atherosclerosis / Q000276:immunology*; D018106:CD28 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000276:immunology*; D005260:Female; D053804:Granzymes / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000096:biosynthesis; D054400:Receptors, CCR7 / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000378:metabolism; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C515370:CCR7 protein, human; D018106:CD28 Antigens; C515187:CXCR3 protein, human; C075005:GNLY protein, human; D008070:Lipopolysaccharides; D054400:Receptors, CCR7; D054367:Receptors, CXCR3; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes