RESUMO
Smoking and exposure to biomass smoke induce the release of pro-inflammatory mediators and the activation of T helper cells. The resulting inflammatory response contributes to the development of COPD. Clinical heterogeneity exists among COPD patients, particularly between patients with disease associated with tobacco smoking (TS-COPD) and those exposed to biomass smoke (BE-COPD). The aim of this study was to identify whether exposure to tobacco and biomass smokes promotes different Th responses that contribute to clinical variability. The study only included women. The frequency of Th17 cells in patients with TS-COPD was significantly higher than in patients with BE-COPD and healthy controls (HC). In contrast, patients with BE-COPD had higher levels of Th2 cells than TS-COPD and HC. In accordance, IL-4 serum concentration was higher in BE-COPD than in TS-COPD. Our data indicates that the different responses induced by these two irritants may underlie the clinical heterogeneity between TS- and BE-COPD patients.
Assuntos
Interleucina-4/imunologia , Nicotiana/imunologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Fumaça/efeitos adversos , Fumar/imunologia , Células Th2/imunologia , Idoso , Biomassa , Feminino , Humanos , Células Th17/imunologia , Nicotiana/efeitos adversosRESUMO
Exposition to tobacco smoke has been established as the main risk factor to develop chronic obstructive pulmonary disease (COPD), by inducing inflammation of the airways. Several cell populations participate in this inflammatory process. It has been accepted that a maladaptive modulation of inflammatory responses plays a critical role in the development of the disease. Regulatory T cells (Treg) are a subset of T CD4(+) lymphocytes that modulate the immune response through secretion of cytokines. The role of the Treg cells in chronic obstructive pulmonary disease is not clearly known, that is why it is important to focus in understanding their participation in the pathogenesis of the disease. To elaborate a systematic review of original articles in which we could describe Treg cells (their ontogeny, mechanisms of action) and their role in COPD, we made a systematic literature search in some data bases (MEDLINE, AMED, PubMed and Scielo) looking through the next keywords: "COPD and Regulatory T cells/EPOC y células T reguladoras", «Inflammation and COPD/Inflamación y EPOC¼, «Regulatory T cells/Células T reguladoras¼. We included basic science articles, controlled and non-controlled clinical trials, meta-analysis and guides. From this search we conclude that Treg cells are a subpopulation of T CD4(+) lymphocytes and their major functions are the suppression of immune responses and the maintenance of tolerance to self-antigens. A disruption in the regulatory mechanisms of the Treg cells leads to the development and perpetuation of inflammation in COPD.
Assuntos
Doença Pulmonar Obstrutiva Crônica/imunologia , Linfócitos T Reguladores/fisiologia , HumanosRESUMO
La exposición al humo del tabaco induce inflamación de las vías aéreas y es el principal factor de riesgo para desarrollar la enfermedad pulmonar obstructiva crónica (EPOC). En este proceso inflamatorio participan varias poblaciones celulares. Algunas fallas en la modulación de la respuesta inflamatoria han sido aceptadas como un factor para el desarrollo de esta enfermedad. Las células T reguladoras (Treg) son un tipo de linfocitos T CD4+ que modulan la respuesta inmune mediante contacto directo con las células efectoras, así como por la secreción de citocinas inmunorreguladoras. El papel de las células Treg en la EPOC no se encuentra completamente comprendido, por lo cual es importante evaluar su participación en la inmunopatogénesis de la enfermedad. Con el objetivo de elaborar una revisión sistemática de artículos originales que nos permitiera describir las células Treg (su origen, características y mecanismos de acción) y su participación en la EPOC, realizamos una búsqueda intencionada en las siguientes bases electrónicas: MEDLINE, AMED, PubMed y Scielo; para ello usamos la combinación de las siguientes palabras clave: <
Exposition to tobacco smoke has been established as the main risk factor to develop chronic obstructive pulmonary disease (COPD), by inducing inflammation of the airways. Several cell populations participate in this inflammatory process. It has been accepted that a maladaptive modulation of inflammatory responses plays a critical role in the development of the disease. Regulatory T cells (Treg) are a subset of T CD4+ lymphocytes that modulate the immune response through secretion of cytokines. The role of the Treg cells in chronic obstructive pulmonary disease is not clearly known, that is why it is important to focus in understanding their participation in the pathogenesis of the disease. To elaborate a systematic review of original articles in which we could describe Treg cells (their ontogeny, mechanisms of action) and their role in COPD, we made a systematic literature search in some data bases (MEDLINE, AMED, PubMed and Scielo) looking through the next keywords: ''COPD and Regulatory T cells/EPOC y células T reguladoras'', <Assuntos
Humanos
, Doença Pulmonar Obstrutiva Crônica/imunologia
, Linfócitos T Reguladores/fisiologia
RESUMO
OBJECTIVE: Previous reports have shown an increase in peripheral blood mononuclear cells' (PBMC) Th17 cell subpopulation and tumor necrosis factor-α (TNF-α) secretion after in vitro stimulation with anti-CD3/CD28 or phorbol myristate acetate/ionomycin in ankylosing spondylitis (AS). The aim of our study was to determine whether there is a Th17 polarization not subjected to in vitro stimulation in patients with AS. METHODS: Nonstimulated PBMC were analyzed from 46 patients with AS, including 7 (15.2%) receiving tumor necrosis factor-α (TNF-α) inhibitors, 20 patients with rheumatoid arthritis, and 25 healthy controls. The surface phenotype of freshly isolated PBMC was determined by flow cytometry. Th1, Th2, Th17, and Treg subsets were defined as CD3+CD4+IFN-γ+, CD3+CD4+IL-4+, CD3+CD4+IL-17A+, and CD3+CD4+FoxP3+, respectively. Serum cytokines and interleukin 8 (IL-8) levels were quantified by Luminex technology. RESULTS: The percentages of Th17 and Th1 cells in AS were higher than in healthy controls (7.4% ± 1.8% vs 0.7% ± 0.2% and 4.0% ± 1.3% vs 1.1% ± 0.3%, respectively; p < 0.0001). Th17 and Th1 cell subsets in patients taking TNF-α inhibitors were lower than in those naive to such therapeutics and similar to healthy controls. Serum levels of IL-6, IL-17A, TNF-α, and IL-8 were significantly higher in patients with AS compared to controls. CONCLUSION: The percentages of Th17 and Th1 cells in PBMC without in vitro stimulation, as well as cytokine and IL-8 levels, were significantly increased in patients with AS compared with healthy controls. These T cell subsets and cytokine profiles of patients with AS taking TNF-α inhibitors were similar to those of healthy controls.
Assuntos
Espondilite Anquilosante/sangue , Espondilite Anquilosante/imunologia , Espondilite Anquilosante/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologia , Adulto , Feminino , Citometria de Fluxo/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Dendritic cells (DC) regulate the activation and differentiation of T cells. They are activated by signals of inflammation and tissue damage, and thus could play a role in the amplification and perpetuation of autoimmune diseases such as systemic lupus erythematosus (SLE). Here we analyzed the phenotype of circulating DC from patients with SLE and studied their differentiation from monocytes. Peripheral blood DC exhibited increased levels of activation in patients with SLE. Although their in vitro differentiation process occurred normally, their responses to activation stimuli (LPS, TNF-α plus PGE(2), anti-CD40) were abnormal when compared to DC differentiated from healthy monocytes. When incubated in the presence of IL-10, DC from patients with SLE were able to induce tolerance to allogeneic antigens in a normal manner. Our results suggest that DC from patients with SLE are abnormal, in part due to the effect of abundant pro-inflammatory signals, but also because of intrinsic cellular defects that alter their responses to activation stimuli.
Assuntos
Diferenciação Celular/imunologia , Células Dendríticas/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Linfócitos T/imunologia , Antígeno B7-1/imunologia , Antígeno B7-1/metabolismo , Antígeno B7-2/imunologia , Antígeno B7-2/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Células Dendríticas/citologia , Células Dendríticas/metabolismo , Dinoprostona/imunologia , Dinoprostona/farmacologia , Citometria de Fluxo , Humanos , Imunofenotipagem , Interleucina-10/imunologia , Interleucina-10/metabolismo , Interleucina-10/farmacologia , Interleucina-6/imunologia , Interleucina-6/metabolismo , Lipopolissacarídeos/imunologia , Lipopolissacarídeos/farmacologia , Lúpus Eritematoso Sistêmico/metabolismo , Modelos Imunológicos , Monócitos/imunologia , Monócitos/metabolismo , Oligopeptídeos , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive disorder characterized by an inflammatory response to cigarette smoke. A disorder in immune regulation contributing to the pathogenesis of COPD has been suggested, however, little is known about the involvement of CD4 (+) T cells. To determine the distribution of different CD4(+) T cell subsets in patients with COPD, current smokers without COPD (CS) and healthy subjects (HS), and its correlation with pulmonary function. METHODS: Th1, Th2, Th17 and Treg, subsets, were quantified by flow cytometry in peripheral blood (PB) of 39 patients with COPD, 14 CS and 15 HS. Correlations were assessed with Spearman's rank test. The association between Th17 and lung function was evaluated with a multivariate logistic regression analysis. RESULTS: An increase of Th17 cells (median 9.7% range 0.8-22.5%) was observed in patients with COPD compared with CS (median 2.8% range 0.8-10.6) and HS (median 0.6% range 0.4-1%, p < 0.0001). Th1 and Tregs subsets were also increased in COPD and CS compared to HS. Inverse correlations were found between Th17 with FEV(1)%p r = -0.57 and with FEV(1)/FVC r = -0.60, (p < 0.0001 for both comparison). In addition, increase of Th17 predicted the presence [OR 1.76 (CI 95% 1.25-2.49, p = 0.001)] and severity of airflow limitation [OR 1.13 (CI95% 1.02-1.25, p = 0.02)]. CONCLUSIONS: The increase of Th17 response and the lost of balance between CD4(+) T cell subsets, suggest a lack of regulation of the systemic inflammatory response that may contribute to pathogenesis in COPD patients.
Assuntos
Interleucina-17/metabolismo , Pulmão/imunologia , Ativação Linfocitária/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Fumar/imunologia , Células Th17/metabolismo , Idoso , Feminino , Citometria de Fluxo , Humanos , Modelos Logísticos , Pulmão/fisiopatologia , Masculino , México/epidemiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fumar/fisiopatologia , EspirometriaRESUMO
The immunological hallmark of SLE is B cell hyperactivity. CD154 (CD40-L) is normally expressed in activated T cells, and plays an important role in T-B interactions. Its expression is increased in SLE T cells. Additionally, its expression on B cells leads to the development of SLE-like disease in a transgenic model. IL-10 is a key cytokine in the disturbed SLE immune system. The aim of this work was to explore the relation between IL-10 and CD154 expression in SLE B cells. We studied 11 SLE patients and 10 healthy volunteers. Mononuclear cells were isolated from peripheral blood and cultured in the presence or absence of Cowan I Strain Staphylococcus (CSS). Surface CD154 and intracytoplasmic IL-10 expression were quantified with flow cytometry. In basal conditions, CD154 expression was not different in patients and controls. B cell stimulation did not cause a significant increase in CD154 expression in control B cells. However, its expression increased 2 times in B cells obtained from SLE patients. IL-10 expression was confined to CD154(+) cells. Our results show that IL-10 production is intimately linked to CD154 expression in B cells, and that the IL-10(+)CD154(+) B cell subset increases abnormally when SLE-derived cells are stimulated with CSS.