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1.
Heliyon ; 10(12): e33143, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39027459

RESUMO

The HLA-B*35 alleles have been associated with a slow or rapid progression of HIV-1 infection. However, the mechanisms related to HIV-1 progression have yet to be entirely understood. Several reports indicate that the binding affinity between the HLA-I molecule and peptides could be associated with an increased CD8+ T-cell response. Novel HLA-B*35-restricted mutated variants have been described from HSNQVSQNY (HY9) and HPVHAGPIA (HA9) epitopes. Bioinformatic analysis has indicated that these mutated epitopes show low and high binding affinity towards HLA-B*35, respectively. However, the polyfunctionality of CD8+ T-cells stimulated with these mutated and wild-type epitopes has yet to be reported. The results suggest that the low-binding affinity H124 N/S125 N/N126S mutated peptide in the HY9 epitope induced a lower percentage of CD107a+CD8+ T-cells than the wild-type epitope. Instead, the high-binding affinity peptides I223V and I223A in the HA9 epitope induced a significantly higher frequency of polyfunctional CD8+ T-cells. Also, a higher proportion of CD8+ T-cells with two functions, with Granzyme B+ Perforin+ being the predominant profile, was observed after stimulation with mutated peptides associated with high binding affinity in the HA9 epitope. These results suggest that the high-affinity mutated peptides induced a more polyfunctional CD8+ T-cell response, which could be related to the control of viral replication.

2.
An Bras Dermatol ; 99(2): 210-222, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38030537

RESUMO

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) develops from epithelial keratinocytes by dysregulation of self-renewal and differentiation. Recent studies have found that the size and number of cSCC tumors gradually decrease or even disappear after HPV vaccination. However, the role of the HPV vaccine in the cSCC mechanism is poorly understood. OBJECTIVE: The aim of this study is to investigate the effect and mechanism of the HPV vaccine in cSCC. METHODS: Immunofluorescence was used to study the immune infiltrating cells in the tumor tissues of patients with cSCC. The effects of the HPV vaccine on cSCC cells and tissues were studied by Cell Culture, Real-time PCR, Western Blot, Cytotoxicity Assay, Enzyme-linked Immunosorbent Assay, m6A Blotting, CCK-8 Assay, m6A Ribonucleic acid Methylation Quantification and tumor transplantation. RESULTS: The HPV vaccine enhanced the toxic effect of CD8+T cells on cSCC cells and promoted the secretion of multiple cytokines by CD8+T cells. In addition, HPV vaccines can increase tumor sensitivity to anti-PD-1 therapy by downregulating METTL3 in tumor tissue, with the combination of HPV vaccine and PD-1 monoclonal antibodies producing enhanced immune cell infiltration compared to PD-1 blockade alone. STUDY LIMITATIONS: It is important to note the limitations of this study, including the small sample size, the construction of the mouse model, and the choice of HPV vaccine and PD-1 monoclonal antibody, which may limit the generalization of our findings to a wider population. CONCLUSIONS: It is hoped that this research will contribute to a deeper understanding of the role of the HPV vaccine in the treatment of cSCC. HPV vaccine is expected to become an important approach to alleviate the development of cSCC.


Assuntos
Carcinoma de Células Escamosas , Vacinas contra Papillomavirus , Neoplasias Cutâneas , Animais , Camundongos , Humanos , Carcinoma de Células Escamosas/patologia , Neoplasias Cutâneas/patologia , Vacinas contra Papillomavirus/uso terapêutico , Receptor de Morte Celular Programada 1 , Imunoterapia , Metiltransferases
3.
An. bras. dermatol ; An. bras. dermatol;99(2): 210-222, Mar.-Apr. 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1556849

RESUMO

Abstract Background Cutaneous squamous cell carcinoma (cSCC) develops from epithelial keratinocytes by dysregulation of self-renewal and differentiation. Recent studies have found that the size and number of cSCC tumors gradually decrease or even disappear after HPV vaccination. However, the role of the HPV vaccine in the cSCC mechanism is poorly understood. Objective The aim of this study is to investigate the effect and mechanism of the HPV vaccine in cSCC. Methods Immunofluorescence was used to study the immune infiltrating cells in the tumor tissues of patients with cSCC. The effects of the HPV vaccine on cSCC cells and tissues were studied by Cell Culture, Real-time PCR, Western Blot, Cytotoxicity Assay, Enzyme-linked Immunosorbent Assay, m6A Blotting, CCK-8 Assay, m6A Ribonucleic acid Methylation Quantification and tumor transplantation. Results The HPV vaccine enhanced the toxic effect of CD8+T cells on cSCC cells and promoted the secretion of multiple cytokines by CD8+T cells. In addition, HPV vaccines can increase tumor sensitivity to anti-PD-1 therapy by downregulating METTL3 in tumor tissue, with the combination of HPV vaccine and PD-1 monoclonal antibodies producing enhanced immune cell infiltration compared to PD-1 blockade alone. Study limitations It is important to note the limitations of this study, including the small sample size, the construction of the mouse model, and the choice of HPV vaccine and PD-1 monoclonal antibody, which may limit the generalization of our findings to a wider population. Conclusions It is hoped that this research will contribute to a deeper understanding of the role of the HPV vaccine in the treatment of cSCC. HPV vaccine is expected to become an important approach to alleviate the development of cSCC.

4.
J Immunother Cancer ; 10(10)2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36220303

RESUMO

BACKGROUND: Colorectal cancer (CRC) has a high mortality rate and can develop in either colitis-dependent (colitis-associated (CA)-CRC) or colitis-independent (sporadic (s)CRC) manner. There has been a significant debate about whether mast cells (MCs) promote or inhibit the development of CRC. Herein we investigated MC activity throughout the multistepped development of CRC in both human patients and animal models. METHODS: We analyzed human patient matched samples of healthy colon vs CRC tissue alongside conducting a The Cancer Genome Atlas-based immunogenomic analysis and multiple experiments employing genetically engineered mouse (GEM) models. RESULTS: Analyzing human CRC samples revealed that MCs can be active or inactive in this disease. An activated MC population decreased the number of tumor-residing CD8 T cells. In mice, MC deficiency decreased the development of CA-CRC lesions, while it increased the density of tumor-based CD8 infiltration. Furthermore, co-culture experiments revealed that tumor-primed MCs promote apoptosis in CRC cells. In MC-deficient mice, we found that MCs inhibited the development of sCRC lesions. Further exploration of this with several GEM models confirmed that different immune responses alter and are altered by MC activity, which directly alters colon tumorigenesis. Since rescuing MC activity with bone marrow transplantation in MC-deficient mice or pharmacologically inhibiting MC effects impacts the development of sCRC lesions, we explored its therapeutic potential against CRC. MC activity promoted CRC cell engraftment by inhibiting CD8+ cell infiltration in tumors, pharmacologically blocking it inhibits the ability of allograft tumors to develop. This therapeutic strategy potentiated the cytotoxic activity of fluorouracil chemotherapy. CONCLUSION: Therefore, we suggest that MCs have a dual role throughout CRC development and are potential druggable targets against this disease.


Assuntos
Colite , Neoplasias Colorretais , Animais , Fluoruracila , Humanos , Mastócitos , Camundongos
5.
AIDS Res Ther ; 19(1): 42, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104716

RESUMO

BACKGROUND: Although combined antiretroviral therapy (cART) has decreased the mortality associated with HIV infection, complete immune reconstitution is not achieved despite viral suppression. Alterations of CD8+ T cells and some of their subpopulations, such as interleukin (IL)-17-producing cells, are evidenced in treated individuals and are associated with systemic inflammation and adverse disease outcomes. We sought to evaluate if different CD8+ T cell subsets are differentially normalized during a clinical follow-up of people living with HIV (PLWH) receiving suppressive cART. METHODS: We explored the changes in the frequencies, activation/exhaustion phenotypes (HLA-DR, CD38, PD-1, and TIM-3), and function (total and HIV-specific cells expressing CD107a, perforin, granzyme B, interferon [IFN]-γ and IL-17) of CD8+ T cells from early-treated PLWH receiving cART in a 1-year follow-up, using a multidimensional flow cytometry approach. RESULTS: Despite continuous cART-induced viral suppression and recovery of CD4+ T cells, after a 1-year follow-up, the CD8+ T cell counts, CD4:CD8 ratio, PD-1 expression, and IL-17 production by CD8+ T cells exhibited incomplete normalization compared with seronegative controls. However, the proportion of CD8+ T cells with an exhausted phenotype (co-expressing PD-1 andTIM-3), and cells co-expressing cytotoxic molecules (Perforin and Granzyme B), reached normalization. CONCLUSIONS: Although suppressive cART achieves normalization of CD4+ T cell counts, only particular subsets of CD8+ T cells are more rapidly normalized in PLWH receiving cART, which could be routinely used as biomarkers for therapy efficiency in these patients.


Assuntos
Infecções por HIV , Linfócitos T CD8-Positivos , Granzimas/metabolismo , Granzimas/uso terapêutico , Humanos , Interleucina-17/metabolismo , Interleucina-17/uso terapêutico , Perforina/metabolismo , Perforina/uso terapêutico , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/uso terapêutico , Subpopulações de Linfócitos T
6.
Rev Med Inst Mex Seguro Soc ; 58(Supl 2): S312-315, 2020 09 21.
Artigo em Espanhol | MEDLINE | ID: mdl-34695345

RESUMO

T lymphocytes (or T cells) are characterized by having an essential role in the control of acute viral infections. SARS-CoV-2 infection is an acute viral infection that mainly affects the respiratory tract causing COVID-19 disease, which presents with mild, moderate and critical symptoms that can lead to the death of the patient. The induction of populations of CD4+ and CD8+ T cell with a functional memory phenotype could be decisive in the control of viral replication and therefore be determinants in the course of the disease. In this opinion article, we will review the reported evidence regarding the presence, phenotype, and function of circulating T cell populations and the site of infection to understand their possible role in controlling viral replication, in the severity of the disease, and the importance of T-cell-mediated protection in the development of vaccines against SARS-CoV-2 infection.


Los linfocitos T se caracterizan por tener un papel esencial en el control de infecciones virales agudas. La infección por SARS-CoV-2 es una infección viral aguda que afecta principalmente el tracto respiratorio y causa la enfermedad COVID-19, la cual cursa con síntomas leves, moderados y críticos que pueden llevar a la muerte del paciente. La inducción de poblaciones de linfocitos T CD4+ y CD8+ con fenotipos de memoria funcionales podrían ser esenciales en el control de la replicación viral y, por lo tanto, determinantes en el curso de la enfermedad. En este artículo de opinión revisaremos las evidencias reportadas en cuanto a la presencia, fenotipo y función de las poblaciones de linfocitos T en circulación y en el sitio de infección para entender su posible papel en el control de la replicación viral, en la severidad de la enfermedad y la importancia de la protección mediada por linfocitos T en el desarrollo de vacunas contra la infección por SARS-CoV-2.

7.
Clin Mol Hepatol ; 26(2): 216-226, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31795627

RESUMO

BACKGROUND/AIMS: Toll-like receptors (TLRs) modulate T cell responses in diverse diseases. Co-stimulation of T cell activation via TLR9 induces production of interferon gamma (IFN-γ), priming of which is critical for differentiation of pro-inflammatory macrophages. These macrophages have a crucial role in nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the expression of TLR9 protein on T cells and the consequences of TLR9-mediated triggering of these cells in patients with NAFLD. METHODS: Our study included 34 patients with simple steatosis, 34 patients with nonalcoholic steatohepatitis, eight patients with NAFLD who met general diagnostic criteria but lacked histological diagnosis, and 51 control subjects. We used a synthetic TLR9 ligand to co-stimulate T cells. We measured TLR9 expression in liver and peripheral T cells and CD69 and IFN-γ as phenotypic markers of T cell activation and differentiation by flow cytometry. RESULTS: TLR9 expression on liver and peripheral T cells was lowest in patients with simple steatosis and was positively associated with anthropometric, biochemical, and histopathological features of NAFLD. In vitro co-stimulation of T cells from patients with simple steatosis induced a limited number of IFN-γ-producing CD8+ T cells. At baseline, these patients showed a low frequency of circulating type 1 CD8+ cells. CONCLUSION: The positive associations between TLR9 and anthropometric, clinical, and histological features and the crucial role of IFN-γ-in NAFLD suggest that limited TLR9 expression and production of IFN-γ play a protective role in patients with simple steatosis.


Assuntos
Linfócitos T CD8-Positivos/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Receptor Toll-Like 9/metabolismo , Adulto , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Estudos de Casos e Controles , Feminino , Humanos , Interferon gama/metabolismo , Ionomicina/farmacologia , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Receptor Toll-Like 9/química
8.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;49(11): e5181, 2016. tab, graf
Artigo em Inglês | LILACS | ID: lil-797892

RESUMO

Osteoarthritis of the knee (kOA) is a disease that mainly affects the elderly and can lead to major physical and functional limitations. However, the specific effects of walking, particularly on the immune system, are unknown. Therefore, this study aimed to analyze the effect of 12 weeks of walking (3×/week) on the leukocyte profile and quality of life (QL) of elderly women with kOA. Sixteen women (age: 67±4 years, body mass index: 28.07±4.16 kg/m2) participated in a walking program. The variables were assessed before and after 12 weeks of training with a progressively longer duration (30–55 min) and higher intensity (72–82% of HRmax determined using a graded incremental treadmill test). The QL was assessed using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), and blood samples were collected for analysis with a cell counter and the San Fac flow cytometer. Walking training resulted in a 47% enhancement of the self-reported QL (P<0.05) and a 21% increase in the VO2max (P<0.0001) in elderly women with kOA. Furthermore, there was a reduction in CD4+ cells (pre=46.59±7%, post=44.58±9%, P=0.0189) and a higher fluorescence intensity for CD18+CD4+ (pre=45.30±10, post=64.27±33, P=0.0256) and CD18+CD8+ (pre=64.2±27, post=85.02±35, P=0.0130). In conclusion, the walking program stimulated leukocyte production, which may be related to the immunomodulatory effect of exercise. Walking also led to improvements in the QL and physical performance in elderly women with kOA.


Assuntos
Humanos , Feminino , Idoso , Contagem de Células Sanguíneas , Terapia por Exercício/métodos , Ativação Linfocitária/fisiologia , Osteoartrite do Joelho/reabilitação , Qualidade de Vida , Caminhada/fisiologia , Avaliação da Deficiência , Citometria de Fluxo , Osteoartrite do Joelho/sangue , Consumo de Oxigênio , Linfócitos T/citologia , Fatores de Tempo
9.
São Paulo; s.n; 2016. [124] p. ilus, graf, tab.
Tese em Português | LILACS | ID: biblio-870892

RESUMO

Líquen plano (LP) é uma doença mucocutânea de natureza inflamatória crônica de etiologia ainda desconhecida. Alterações na resposta imune inata, como aos padrões moleculares associados à patógenos (PAMPs) e padrões moleculares associados ao dano (DAMPs) podem levar à inflamação crônica e contribuir com a patogênese do LP. OBJETIVO: Avaliar o efeito da ativação via o DAMP S100A8 e o receptor Toll-like 4 (TLR-4) em células Natural killer (NK) e TCD8 citotóxicas e suas subpopulações de memória/efetoras em pacientes com LP. MÉTODOS: Foram selecionados 25 pacientes com LP (22 mulheres, 3 homens) com idade média de 43,46 anos ± 8,46 e um grupo controle com 25 indivíduos (22 mulheres, 3 homens) com idade média de 42 anos ± 5,5. A determinação transcricional e da expressão por imunohistoquimica dos DAMPs S100A8, HMGB-1 e de TLR-4 e RAGE foi realizada em biópsias de lesões cutâneas de indivíduos com LP, e os níveis séricos de S100A8, HMGB-1, MICA e MICB foram determinados por ELISA. As células mononucleares (CMNs) de sangue periférico foram avaliadas por citometria de fluxo quanto a frequência de TNF, IL-1beta e o marcador de desgranulação CD107a em células TCD8+ e células NK CD56+ e suas subpopulações. A avaliação da via de sinalização de TLR em células TCD8+ purificadas e ativadas com S100A8 foi analisada por PCR array e a determinação da expressão de mRNA dos componentes do inflamassoma em células TCD8+ ativadas com S100A8 por PCR em tempo real. RESULTADOS: Foi evidenciado nos indivíduos com LP elevada expressão da proteína S100A8 nas lesões cutâneas e de HMGB-1, TLR-4 e RAGE na derme, em paralelo ao aumento da expressão de mRNAs para S100A8 e S100A9 e diminuição de RAGE. Além disto, uma elevação dos níveis séricos do dímero S100A8/A9 foi detectada nos pacientes comparados aos controles, ao contrário do DAMP HMGB-1 que mostrou níveis similares em ambos os grupos. A influência do S100A8 em células TCD8+ e células NK, foi analisada em CMNs pela ativação...


Lichen planus (LP) is a mucocutaneous inflammatory chronic disease of unknown etiology. Alterations in the innate immune response such as the pathogen-associated molecular pattern (PAMPs) and damage-associated molecular pattern (DAMPs) can lead to chronic inflammation and contribute to the pathogenesis of LP. OBJECTIVE: Evaluate the effect of the activation trough the DAMP S100A8 and the Toll-like receptor 4 (TLR-4) on the Natural killer cells (NK) and cytotoxic TCD8 cells and their memory / effector subsets in LP disease. METHODS: We selected 25 patients with LP (22 women, 3 men) with a mean age of 43.46 years ± 8.46 and a control group of 25 subjects (22 women, 3 men) with a mean age of 42 ± 5, 5. The transcriptional determination and protein expression by immunohistochemistry of DAMPs, S100A8 and HMGB-1 as well as TLR-4 and RAGE was performed on biopsies of skin lesions from patients with LP, and serum levels of S100A8, HMGB-1, MICA and MICB were determined by ELISA. Peripheral blood mononuclear cells (PBMCs) were assessed by flow cytometry to evaluate the frequency of TNF, IL-1beta and the degranulation marker CD107a in CD8+ T cells and CD56 + NK cells and their subsets. The evaluation of the TLR signaling pathway in purified CD8 + T cells activated with S100A8 were analyzed by PCR array and the determination of mRNA expression of inflammasome components on CD8 + T cells activated by S100A8 was measured by real time PCR. RESULTS: It was shown in the LP individuals an increased expression of the S100A8 protein in the cutaneous lesions and HMGB-1, TLR-4 and RAGE in the dermis, in parallel to increased level of mRNAs for S100A8 and S100A9 and decreased expression of RAGE. Moerover, increased serum levels of the dimer S100A8 / A9 was detected in patients compared to controls, in contrast to DAMP HMGB1 that revealed similar levels in both groups. The influence of S100A8 in CD8 + T cells and NK cells, was analyzed in PBMC activating with...


Assuntos
Humanos , Masculino , Feminino , Peptídeos Catiônicos Antimicrobianos , Células Matadoras Induzidas por Citocinas , Citotoxicidade Imunológica , Líquen Plano
10.
Sci. med ; 24(3): 224-228, jul-set. 2014. tab
Artigo em Português | LILACS-Express | LILACS | ID: lil-743663

RESUMO

Objetivos: Avaliar o perfil imunológico de risco em idosas com câncer de mama e testar se este pode ser um fator preditivo confiável para determinar tipos de tratamento e seguimento oncológico.Métodos: Foram pesquisadas a relação das células T CD4+/CD8+ e a sorologia para citomegalovírus no sangue periférico de mulheres com 60 anos ou mais de idade no momento do diagnóstico da neoplasia mamá¡ria, que realizaram tratamento cirúrgico no Centro de Mama da Pontifí­cia Universidade Católica do Rio Grande do Sul pelo Sistema Único de Saúde. Foram excluí­das da pesquisa pacientes com sorologia positiva para HIV, com imunossupressão após transplante de órgãos e as que realizaram quimioterapia neoadjuvante. Os dados foram comparados em grupos conforme o comprometimento axilar, o tamanho tumoral, o perfil imunohistoquí­mico do tumor e a ocorrência de eventos adversos (recidiva axilar, recidiva local do tumor e/ou metástases). Nos casos de eventos adversos, foi realizada uma nova contagem de CD4+ e CD8+.Resultados: Foram incluídas 37 pacientes, entre as quais 10 tiveram metástases axilares. As pacientes com axila positiva para metástases apresentaram uma relação CD4+/CD8+ maior que nos casos de axila negativa para metástases (p=0,04). Não foi encontrada diferença estatisticamente significativa em relação ao tamanho e perfil imunohistoquí­mico do tumor. No seguimento médio de 14,3 meses, ocorreram dois eventos adversos (uma recidiva axilar e um caso de metástases ósseas), quando se observou um aumento na relação das células T pesquisadas.Conclusões: A relação das células T CD4+/CD8+ parece aumentar nos casos de câncer de mama de pior prognóstico. Tanto quanto foi possível pesquisar na literatura, estes são os primeiros dados sobre células T CD4+ e CD8+ no sangue periférico de mulheres idosas com câncer de mama. Um seguimento maior poderá determinar o valor destas células como fator prognóstico e/ou preditivo.


Aims: To evaluate the immune risk profile of elderly women with breast cancer and to assess whether this can be a reliable predictor to determine types of treatment and oncologic follow-up.Methods: We assessed the CD4+/CD8+ ratio in peripheral blood cell, as well as serology for cytomegalovirus, of 37 women who were aged 60 years or more at the time they were diagnosed with breast cancer/. They all had surgical treatment at the Breast Center from Pontificia Universidade Catolica do Rio Grande do Sul. Those with positive serology for HIV, or immuno suppressed due to organ transplant, as well as those who had neoadjuvant chemotherapy. Data was analyzed according to axillary involvement, tumor size, tumor immunohistochemical profile and occurrence of adverse events (axillary relapse, local relapse and/or metastases).Results: The mean value of CD4+/CD8+ ratio was 1.72 (min. 1.1, max. 2.32) and cytomegalovirus serology was positive in all subjects. Comparing the groups, patients with positive axillary metastases (n=10) had a CD4+/CD8+ ratio greater than in those with negative axillary metastases (p=0.04). No statistically significant difference was detected regarding the size and immunohistochemical profile of the tumor. Two adverse events occurred at a mean follow-up of 14 months (one axillary relapse and one bone metastasis), when an increase in the CD4+/CD8+ ratio was observed.Conclusions: The CD4+/CD8+ ratio appear to increase in cases of breast cancer with worst prognosis. As far as was possible to search, these are the first data on CD4+ and CD8+ peripheral blood of elderly women with breast cancer. A longer follow-up will determine the value of these cells as a prognostic and/or predictive marker.

11.
An. bras. dermatol ; An. bras. dermatol;88(6): 954-960, Nov-Dec/2013. graf
Artigo em Inglês | LILACS | ID: lil-698990

RESUMO

Several distinct clinical forms of mycosis fungoides have been described. Hypopigmented mycosis fungoides should be regarded as a subtype of mycosis fungoides, insofar as it presents some peculiar characteristics that contrast with the clinical features of the classical form. Most patients with hypopigmented mycosis fungoides are younger than patients typically diagnosed with classical mycosis fungoides. In addition to typical dark-skinned individuals impairment, hypopigmented mycosis fungoides has also been described in Asian patients. The prognosis for hypopigmented mycosis fungoides is much better than for classical mycosis fungoides: hypopigmented mycosis fungoides is diagnosed when there are only patches of affected skin, and lesions usually will not progress beyond terminal stages, although they can persist for many years. Diagnosis should involve clinicopathologic correlation: skin biopsy analysis often reveals intense epidermotropism, characterized by haloed, large, and atypical CD8+ lymphocytes with convoluted nuclei, in contrast to mild to moderate dermal lymphocytic infiltrate. These CD8+ cells, which participate in T helper 1-mediated immune responses, prevent evolution to mycosis fungoides plaques and tumors and could be considered the main cause of the inhibition of melanogenesis. Therefore, hypopigmentation could be considered a marker of good prognosis for mycosis fungoides.


Ultimamente diferentes formas clínicas da micose fungoide têm sido descritas. A micose fungoide hipocromiante pode ser considerada um subtipo da micose fungoide, apresentando algumas características peculiares que contrastam com os achados da forma clássica da micose fungoide. A maioria dos pacientes com micose fungoide hipocromiante são mais jovens que aqueles acometidos pela micose fungoide clássica. Esta variante é descrita principalmente em indivíduos melanodérmicos (afroamericanos e asiáticos). O prognóstico é melhor que o observado para a forma clássica: ao diagnóstico, os pacientes apresentam somente "patches", que tendem a perdurar por longos períodos, sem evolução para estágios mais avançados. O diagnóstico é feito através da correlação clinicopatológica: biópsia da lesão cutânea frequentemente revela intenso epidermotropismo, caracterizado por linfócitos CD8+ atípicos, grandes, com halo e núcleo convoluto, contrastando com o infiltrado dérmico leve a moderado. Estas células CD8+, que participam do perfil de resposta T helper-1, impediriam a evolução da doença para o desenvolvimento de placas infiltradas e tumores, além de determinar a inibição da melanogênese nas lesões hipocrômicas. Portanto, a hipocromia poderia ser considerada um marcador de bom prognóstico na micose fungoide.


Assuntos
Feminino , Humanos , Masculino , Hipopigmentação , Micose Fungoide , Neoplasias Cutâneas , Biópsia , /imunologia , /patologia , Hipopigmentação/imunologia , Hipopigmentação/patologia , Hipopigmentação/fisiopatologia , Micose Fungoide/imunologia , Micose Fungoide/patologia , Micose Fungoide/fisiopatologia , Prognóstico , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/fisiopatologia
12.
Acta cir. bras. ; 22(3): 215-219, May-June 2007. graf
Artigo em Inglês | VETINDEX | ID: vti-2260

RESUMO

PURPOSE: To evaluate the effects of glutamine (L-Gln) or whey-protein supplementation on CD4+ and CD8+ lymphocytes in alloxan-induced diabetic rats. METHODS: Thirty-two healthy male Wistar rats were used in the experiment. Eight rats served as baseline controls (G-1). The remaining 24 animals received alloxan 150mg/Kg intraperitonially dissolved in buffer solution and were equally distributed in 3 subgroups, upon induction of diabetes mellitus, and treated as follows: (G2): saline, 2.0ml; (G3): glutamine solution (0.7g/kg), 2.0 ml; and (G4): whey-protein (WPS) solution (0.7g/kg), 2.0 ml. All solutions were administered by daily 7:00 AM gavages during 30 days. Next, arterial blood samples (3.0 ml) were collected from anesthetized rats for CD4+ and CD8+ lymphocyte count through flow cytometry technology. RESULTS: CD4+ and CD8+ counts decreased significantly in all groups compared with baseline values (G1). G2 rats CD4+/CD8+ ratio decreased significantly compared with G1. CD4+/CD8+ ratio increased significantly (>260 percent) in L-Gln treated group (G3) compared with saline-treated rats (G2). There were no statistical differences in lymphocyte counts (CD4+ and CD8+) between L-Gln (G3) and saline-treated (G2) groups. There was a significant reduction in CD8+ cell count compared with CD4+ cell count in L-Gln treated rats (G3). CONCLUSION: The offer of L-Gln to experimental diabetic rats enhances the immunologic response to infection.(AU)


OBJETIVO: Avaliar os efeitos da suplementação de glutamina ou proteína do soro de leite ( PSL) sobre os linfócitos CD4+ e CD8+ em ratos diabéticos aloxano induzidos. MÉTODOS: Trinta e dois ratos Wistar machos, saudáveis, foram utilizados no estudo. Oito ratos foram usados como controles basais (G1). Os 24 animais remanescentes foram equitativamente distribuídos em 3 subgrupos, após indução do diabetes mellitus por injeção intraperitonial de aloxano (150mg/Kg) e tratados como se segue: (G2): salina; (G3): 2,0 ml de solução de glutamina (0,75g/Kg);(G4): PSL, (0,7g/Kg), 2,0ml. Todas as soluções foram administradas por gavagem, diariamente, cada 7:00 h, durante 30 dias. Após esse período, foram coletadas amostradas de sangue arterial para contagem de linfócitos CD4+ e CD8+ por citometria de fluxo. RESULTADOS: A população de linfócitos CD4+ e CD8+ diminuiu significantemente em todos os grupos em comparação aos valores encontrados no grupo G1. A razão CD4+/CD8+ foi significantemente maior (>260 por cento) nos ratos tratados com L-Gln que nos ratos tratados com salina (G2). Não se observaram diferenças significantes na população de linfócitos CD4+ e CD8+ entre os grupos G3 e G2. Houve redução significante do número de células CD8+ quando comparado ao número de células CD4+ nos ratos tratados com L-Gln (G3). CONCLUSÃO: A oferta de L-Gln em ratos diabéticos aloxano-induzidos melhora a resposta imunológica à infecção.(AU)


Assuntos
Animais , Masculino , Glutamina/efeitos adversos , Glutamina/análise , Suplementos Nutricionais/efeitos adversos , Camundongos Endogâmicos NOD
13.
Rev. cuba. med ; 37(1): 28-35, ene.-mar. 1998.
Artigo em Espanhol | LILACS | ID: lil-628790

RESUMO

Se estudió la función que desempeña el antígeno leucocitario humano (HLA-B27) en la patogénesis de las espondiloartropatias seronegativas. Se describió detalladamente la zona de unión de péptidos de la molécula conocida como «bolsón 45». Como hipótesis actuales en el surgimiento de la enfermedad se discutieron la mímica molecular entre bacterias artritogénicas y HLA-B27, la positividad del HLA-B27 y la persistencia de las infecciones enterobacteriales, HLA-B27 factores modificantes y el modelo del péptido artritogénico. Se explicó la función de la célula T CDB+ en el desencadenamiento de la enfermedad y su control por los linfocitos T CD4+.


The function of HLA-B27 in the pathogenesis of seronegative spondyloarthropathies was studied. The zone of union of the peptides of the molecule known as «big pocket 45» was described in detail. The molecular mimicry between arthritogenic bacteria and HLA-B27, the positivity of HLA-B27 and the persistance of enterobacterial infections, the HLA-B27 modifying factors, and the model of arthritogenic peptide were discussed as present hypotheses connected with the appearance of the disease. The function of the CDB-positive T-cell in the outbreak of the disease, as well as its control by the CD4-positive T-lymphocytes was explained.

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