18 resultados para TCD8
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The most common malignant neoplasm of the oral cavity and oropharynx are squamous cell carcinoma. Injuries to the same stage and subjected to the same treatment protocol have sometimes different evolutionary courses. The scope of this study was to investigate, through a retrospective cohort, associations between the number of CD8 + T cells and natural killer, identified immunohistochemically in the inflammatory infiltrate in a series of cases of oral squamous cell carcinoma and orofaringeano, and the level of tumor response to radiotherapy and chemotherapy, overall survival and relapse-free survival of patients. We identified 54 patients with unresectable disease were treated exclusively with radiotherapy and chemotherapy. The median follow-up was 22 months. The sample was characterized by the predominance of male subjects, median age 60 years, all were smokers. The most frequent site was the tongue and 81.5% were in stage IV. Patients with disease in the oral cavity had a worse response to treatment (p = 0.006), worse relapse-free survival (p = 0.007), worse overall survival (p = 0.007). The advanced T stage was shown a negative prognostic factor (p= 0.006) for the clinical treatment response made. Immunohistochemistry was performed to select CD8 + cells (anti-CD8) and NK cells (anti-CD57). Lymphocytes positive and negative markings were counted using the program ImageJ . Two groups were created for each marking evaluated: Group I patients with more than 50% cells positive, Group II: less than 50% of labeled cells. For CD8 + cells detected in 38 (70.3%) of Group I were CD8 + and 16 (29.7%) Group II CD8 +. For NK cells, 26 (48.15%) Group I NK and 28 (51.85%) Group II NK. Regarding the clinical response to treatment, we observed that 39% of patients achieved a complete response and 25.9% remained without recurrence at the end of follow-up. These results were better in Group I CD8 + (p = 0.2). Identified that 72.2% of patients progressed to death, this finding had no association with the immunohistochemical data. There was no statistically significant differences between the number of CD8 + and NK cells and the ability of tumor response to radiotherapy and chemotherapy, or with overall survival and relapse-free survival of patients. However, especially in relation to a learned response, we found that this group of patients with advanced disease have a low count of CD8 + T cells active. Believing in the role that the immune response plays in the local fight against neoplastic cells, however, our results do not support the use of quantitative analysis of CD8 + T cells and NK cells as a prognostic factors for oral squamous cell carcinoma and oropharynx
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Trypanosoma cruzi trypomastigotes continuously shed into the medium plasma membrane fragments sealed as vesicles enriched in glycoproteins of the gp85 and trans-sialidase (TS) superfamily and alpha-galactosyl-containing glycoconjugates. Injection of a vesicle fraction into BALB/c mice prior to T. cruzi infection led to 40% of deaths on the 16th day post-infection and 100% on day 20th whereas 20% of untreated animals survived for more than 30 clays. The vesicle-treated animals developed severe heart pathology, with intense inflammatory reaction and higher number of amastigote nests. Analysis of the inflammatory infiltrates 15 days after infection showed predominance of TCD4(+) lymphocytes and macrophages, but not of TCD8(+) cells, as well as a decrease of areas labeled with anti-iNOS antibodies as compared to the control. Higher levels of IL-4 and IL-10 mRNAs were found in the hearts and higher IL-10 and lower NO levels in splenocytes of vesicles pretreated animals. Treatment of mice with neutralizing anti-IL-10 or anti-IL-4 antibodies precluded the effects of pre-inoculation of membrane vesicles on infection. These results indicate that T. cruzi shed membrane components increase tissue parasitism and inflammation by stimulation of IL-4 and IL-10 synthesis and thus may play a central role in the pathogenesis of Chagas` disease acute phase. (c) 2008 Elsevier Masson SAS. All rights reserved.
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Iron is an essential element for many cellular functions, including the immune response against intracellular pathogens. In this study, we aimed evaluate the effect of iron on IRP2, IFN-γ, TNF-α, IL-6, IL-10, MIG and IP10 expression in PBMC and assess the effect of the spleen parasite load on the expression of these genes in the spleen of L. infantum naturally infected dogs. Blood sample from 7 DTH+ donor was collected and PBMC was obtained. The cells were cultivated in absence (iron chelator desferroximane, DFO 10 μM supplemented media) or in presence of iron (hemin 6 mM) for 1 h, followed by stimulation with Leishmania infatum antigen for 4 h. 44 dog spleen samples were obtained and parasite load in this organ was determinate by qPCR. Gene expression was analyzed by qPCR and cytokine production quantified by flow cytometry. In antigen stimulated cells, genes involved in immune response are significantly more expressed in presence of iron. T CD4+ and TCD8+ lymphocytes produces IFN-γ, TNF-α and IL-10 possibly in iron dependent pathway. Monocytes antigen stimulated reduced TNF-α, IL-6 and IL-10 production in presence of iron. We found spleen of infected dogs IRP2 expression increases according to parasite load in that organ, while an inverse profile was found for IFN-γ, TNF-α e IL-10 expression. These results suggest that T lymphocytes depends on iron to produce IFN-γ, TNF-α and IL-10, while iron seems to inhibit cytokine production in monocytes. So, we propose an immunoregulatory mechanism carried out by iron during L. infantum infection in humans and dogs
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O cncer de colo uterino consiste em um problema de grande relevncia social, visto que se trata da segunda malignidade ginecolgica mais freqente no mundo. O principal precursor do cncer da crvice uterina consiste na infeco pelo Papiloma vrus humano (HPV). O HPV tem despertado grande interesse na comunidade cientfica, devido relao estabelecida entre a sua epidemiologia e o cncer de crvice uterina. Apesar do grande avano na biologia do HPV, pouco se sabe acerca da resposta imunolgica a este vrus. O Papilomavrus humano (HPV) um DNA vrus epiteliotrfico, que est vinculado carcinognese do colo uterino por meio de evidncias epidemiolgicas e laboratoriais. As infeces pelo HPV ocorrem em mulheres em todo o mundo. Existe consenso na literatura quanto associao do DNA HPV com as neoplasias intra epiteliais cervicais e o cncer cervical. Por este motivo de grande importncia a deteco precoce deste tipo de infeco para que seja efetuado um tratamento especfico. Esse trabalho est caracterizando o perfil imunolgico de pacientes portadoras de HPV atravs da quantificao linfocitria (TCD4, TCD8, clulas NKT e clulas NK), e correlacionou esse material tcnica de captura hbrida, para poder comprovar a infeco pelo HPV, esperando assim contribuir precocemente para o diagnstico do cncer de colo uterino.
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The presence of inflammatory cells within the tumor microenvironment plays a dual role that may contribute both to the progression and for inhibition of tumor growth. Recent studies suggest that the quality, not the quantity, of the inflammatory infiltrate is the most important determinant for prognosis. Therefore, TCD8 cells and natural killer cells are the main effector cells in combating cancer. The aim of this study was to assess, through the immunohistochemical study, the expression of TCD8 lymphocytes and NK cells in epidermoid carcinoma (EC) of the lower lip. The sample consisted of 32 specimens of EC of the lower lip, of which 16 had regional lymph node metastasis, and the 16 remaining, free of metastases. The total number of positive cells at the front of invasion were evaluated quantitatively and the results were related to clinical TNM staging, histological grade of malignancy and prognostic factors. It was observed for the group with metastasis, prevalence of stages III and IV (p<0.0001). Most patients with metastasis, had a high grade of malignancy (p=0.006). Most cases classified as high grade of malignancy had stages III and IV (p=0.032). Of the total sample, there were three cases of recurrence and five with death, however these variables were not statistically significant when associated with clinicopathological parameters. The immunostaining of CD8 and CD57, respectively, showed no statistically significant association with any of the clinicopathological parameters studied, metastasis (p=0.346, p=0.622), TNM classification (p=0.146, p=0.576), histological grade of malignancy (p=0.936, p=936), recurrence (p=0.075, p=0.075) and death (p=0.897, p=0.856). Believing in the function of the immunological system against malignant cells, it is concluded that the TD8 lymphocytes and NK cells, would be acting in the control of the progression of malignant neoplasms, but not in isolated manner
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Snake venoms have been used as antineoplastic substances in several experimental models. We demonstrated in previous studies that Bothrops jararaca venom (BjV) induces inhibition of Ehrlich ascites tumor ( EAT) growth accompanied by an increase of mononuclear (MN) leukocytes in all groups inoculated with EAT and/or venom. The objective of the present study was to characterize the subpopulations of MN leukocytes involved in the inhibition of EAT growth by treatment with BjV. Swiss mice were inoculated with 1.0 x 10(3) EAT cells by the intraperitoneal route and treated with 0.4 mg/kg of BjV by the same route ( Group TV). Treatment was started 24 h after tumor cell inoculation and consisted of five intraperitoneal injections performed at 72 h intervals. After 2, 8 and 14 days, groups of animals were sacrificed and the number of B, TCD4 and TCD8 lymphocytes, macrophages and natural killer cells present in the peritoneal cavity was determined by flow cytometry. The control group consisted of animals inoculated with EAT and treated with 0.1 ml of saline under the same conditions as the experimental group ( Group T). Two additional control groups consisted of animals not inoculated with EAT and treated with saline or venom. Data were analyzed statistically by the Kruskal - Wallis nonparametric test for independent samples. on the 2nd and 8th day we observed a difference between groups T and TV ( group T > group TV) for all cell types, except natural killer cells, that only differed on the 2nd day. However, on the 14th day there was no difference in MN cells among groups. These data suggest that the inhibition of EAT is related to the toxic action of BjV on tumor cells and/or to the proteolytic effect of the venom on the mediators produced by the cells for growth modulation.
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HIV patients are predisposed to the development of hypertriglyceridemia and hypercholesterolemia as a result of both viral infection and HIV infection therapy, especially the protease inhibitors. Chemokines and cytokines are present at sites of inflammation and can influence the nature of the inflammatory response in atherosclerosis. We investigated the correlation between biochemical variables and -chemokines (MIP-1 and RANTES) and the apolipoprotein E genotype in HIV-infected individuals. The apolipoproteins were measured by nephelometry. Triglycerides and total cholesterol were determined by standard enzymatic procedures. The -chemokines were detected by ELISA. The genetic category of CCR5 and apolipoprotein E were determined by PCR amplification and restriction enzymes. Immunological and virological profiles were assessed by TCD4 + and TCD8 + lymphocyte counts and viral load quantification. Positive correlations were found between apo E and CD8 + (p = 0.035), apo E and viral load (p = 0.018), MIP-1 and triglycerides (p = 0.039) and MIP-1 and VLDL (p = 0.040). Negative correlations were found between viral load and CD4 + (p = 0.05) and RANTES and CD4 + (p = 0.029). The -chemokine levels may influence lipid metabolism in HIV-infected individuals. 2005 by The Brazilian Journal of Infectious Diseases and Contexto Publishing. All rights reserved.
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Visceral leishmaniasis in dogs is described as a chronic disease whose main symptoms are progressive weigth loss, cachexy and dermatologic lesions. Recently, the disease has been associated to neurologic disorders. A total of 40 dogs with visceral leishmaniasis were divided into two groups. The first composed of dogs without neurological signs (n=30) and the second by dogs with neurological disorders (n=10). Brain samples were collected, stored in 10% buffered formalin and subjected to immunohistochemical examination for amastigotes forms of Leishmania (Leishmania) infantum chagasi, CD3+, CD4+ and CD8+ T lymphocytes and macrophages. Imunnohistochemistry evaluation revealed no amastigote forms of the parasite. CD3+ T lymphocytes were present in 24/30 (80%) dogs without neurological signs and in all dogs from the second group (p=0.0011). CD4+ and CD8+ were rarely observed, with CD4+ immunostaining in 10/40 (25%) dogs, from which half of them had neurological disease (p=0.0090). The presence of CD8+ was detected only in 4/10 (40%) dogs from neurological group (p=0.0021). Macrophages were detected in 38/40 (95%) dogs, without significant differences between groups (p=0.7664).
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Coordenao de Aperfeioamento de Pessoal de Nvel Superior (CAPES)
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A cromoblastomicose (CBM) uma doena fngica crnica que acomete a pele, caracterizada pelo desenvolvimento de leses polimrficas, que apresentam infiltrado inflamatrio granulomatoso na presena de clulas esclerticas, patognomnicas desta doena. Um dos objetivos deste estudo foi avaliar a induo de clulas esclerticas por meios naturais, com biomassas de Bactris gasipaes e de Theobroma grandiflorum, cujas respectivas espcies induziram in vitro clulas esclerticas similares quelas encontradas nos tecidos de leses humanas, em 10 e 2 dias, respectivamente, o que viabilizou a produo de um meio indutor em p, j disponibilizado a outros grupos que estudam a CBM. Outro objetivo foi avaliar a imunopatologia da CBM nos pacientes, antes e durante a utilizao de itraconazol (ITZ). Para isto, foi utilizada a tcnica de ELISA para as citocinas TNF-, IL-4 e IL-10 circulantes, e a imunohistoqumica de bipsias das leses em diferentes tempos de tratamento que permitiu analisar as alteraes quantitativas e qualitativas dos tipos celulares durante 12 meses do tratamento com ITZ na dose de 200 mg/dia com anticorpos anti-CD20, anti-CD8 e anti-CD68. Quanto as citocinas, a IL-10 circulante no mostrou nenhuma mudana significativa, enquanto IL-4 e TNF- apresentaram um aumento da titulao ao longo de 12 meses de tratamento. Em relao imunofenotipagem, houve uma diminuio significativa no processo inflamatrio e nos infiltrados celulares durante 3 e 6 meses do tratamento, enquanto que apenas aos 12 meses houve a regresso significativa do nmero de esclerticas. A Imunofenotipagem revelou que os macrfagos esto localizados principalmente nas reas centrais do granuloma, enquanto que as clulas TCD8+ esto na periferia e as clulas TCD20+ encontram-se homogeneamente distribudas, com um aumento significativo aps 6 meses do tratamento, retornando aos nveis iniciais aps um ano. Os macrfagos e linfcitos citotxicos so recrutados para o stio de infeco durante o tratamento, apresentando um aumento significativo aps 12 meses de tratamento com ITZ. Estes resultados demonstram que a formao do granuloma na CBM semelhante queles observados em outras doenas infecciosas granulomatosas, e que a presena de IL-4 e IL-10 podem estar relacionadas com a persistncia do fungo nas leses e com a dificuldade de cura observada nestes pacientes.
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No presente estudo foram investigadas as freqncias dos polimorfismos nos genes FAS e FASL em um grupo de 198 indivduos soropositivos para o HIV-1 e 191 indivduos controles soronegativos, com o objetivo de avaliar a ocorrncia de uma possvel associao entre os polimorfismos nestes genes e a infeco pelo HIV-1. A identificao dos alelos A e G do polimorfismo -670 FAS foi realizada por meio da tcnica de PCR, utilizando seqncias de iniciadores especficos e posterior digesto enzimtica (RFLP) com a enzima MvaI. A identificao dos alelos A e G do polimorfismo -124 FASL, bem como T e delT do polimorfismo -169 FASL foi realizada atravs da tcnica de ACRS, seguido de RFLP com as endonucleases de restrio FokI e HincII, respectivamente. As anlises das freqncias allicas e genotpicas dos polimorfismos analisados no mostraram qualquer diferena significativa entre soropositivos e soronegativos. A anlise da quantificao dos linfcitos T CD4<sup>+</sup> entre os portadores dos diferentes gentipos do polimorfismo -670 FAS revelou uma associao significativa, sugerindo que o estado de portador do alelo G, em homo ou heterozigose, nos indivduos infectados pelo HIV-1 pode ser um fator de proteo depleo destas clulas no curso da infeco pelo HIV-1. As associaes entre o nmero de linfcitos TCD8<sup>+</sup>, a carga viral plasmtica e os polimorfismos analisados no foram estatisticamente significantes. Desse modo, pode-se sugerir, que o polimorfismo -670 do gene FAS, influencie na apoptose dos linfcitos T CD4<sup>+</sup> no curso da infeco pelo HIV-1, assim, faz-se necessrio estudos adicionais visando confirmar ou no esta associao, uma vez que a identificao desse polimorfismo pode ser, no futuro, uma importante ferramenta a ser utilizada no acompanhamento da infeco.
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Coordenao de Aperfeioamento de Pessoal de Nvel Superior (CAPES)
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Considering the importance of umbilical cord blood as a potential source of stem cell and, on the other hand, the use of the domestic swine (Sus scrofa) as a useful model for biomedical research in regenerative medicine and aiming to contribute about the quantification of lymphocyte subsets in umbilical cord blood and peripheral blood of newborn piglets, this study aimed to quantify CD4+, CD5+ and CD8+ cells from umbilical cord blood and peripheral blood from pigs at term blood samples. Were analyzed samples of the umbilical cord blood and peripheral of 48 piglets of Topigs lineage, from healthy mothers, artificially inseminated and natural birth. Blood samples were collected from the umbilical cord at birth, by the umbilical vein, and peripheral blood by venous sinus retro-ophthalmic. The immunological measurements of CD4+, CD5+ and CD8+ were obtained by flow cytometry. The relative average values for the CD4+, CD5+ e CD8+ counts in umbilical cord blood and peripheral blood of newborn piglets were inferior to those reported for peripheral blood in adult pigs, suggesting immunological immaturity. The ratio CD4+:CD8+ in umbilical cord blood (3.21.2%) and peripheral blood (3.21.7%) showed a predominance of TCD4+ over TCD8+. The percentage of CD4+ and CD8+ cells was 1.370.86% and 1.150.57%, respectively, in umbilical cord blood and peripheral blood.
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Ps-graduao em Medicina Veterinria - FCAV
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The direct killing of target cells by cytotoxic T lymphocytes (CTLs) plays a fundamental role in protective immunity to viral, bacterial, protozoan and fungi infections, as well as to tumor cells. In vivo cytotoxic assays take into account the interaction of target and effector cells in the context of the proper microenvironment making the analysis biologically more relevant than in vitro cytotoxic assays. Thus, the development, improvement and validation of in vivo methods are necessary in view of the importance of the results they may provide. We describe and discuss in this manuscript a method to evaluate in vivo specific cytotoxic T lymphocyte killing. We used as model system mice immunized with human recombinant replication-deficient adenovirus 5 (HAd5) containing different transgenes as the trigger of a CTL-mediated immune response. To these mice, we adoptively transferred syngeneic cells labeled with different vital fluorescent dyes. Donor cells were pulsed (target) or not (control non-target) with distinct CD8 T-cell epitopes, mixed in a 1:1 ratio and injected i.v. into immunized or non-immunized recipient mice. After 18-24h, spleen cells are collected and analysed by flow cytometry. A deviation from the 1:1 ratio of control and target cell populations indicates antigen specific lysis of target cells
