Regulatory B cells in an experimental model of type 1 diabetes

Regulatory B cells, producing IL-10, have been studied in many autoimmune diseases. However, less is known about these cells in Type 1 diabetes (T1D), a disease characterized by the destruction of beta-cells by the immune system, leading to deficient production of insulin. Although B cells play a role in development of T1D, most previous investigations have focused on their pathogenic involvement. B cell depletion has been shown to be protective against diabetes development. To examine regulatory B cells in T1D, we used Non-Obese Diabetic (NOD) mice and non-diabetes-prone B6g7 mice as controls. We compared both strains for the production of cytokines and expression of putative regulatory phenotypes in spleen B cells cultured with various stimulants, at different ages. We observed that NOD mice that were > 35 weeks old and naturally protected against T1D had more IL-10-producing B cells than B6g7 and diabetic NOD mice, and this number increased even more on stimulation with lipopolysaccharide (LPS) stimulation. When LPS-stimulated B cells from protected mice were cultured in vitro with CD8 T cells and DCs, their potential for suppression of T cell cytotoxic activity was higher than unstimulated B cells and B cells from diabetic mice. This inhibitory effect was associated with higher levels of IL-10. Lastly, we carried out an investigation where B cells were transiently depleted in transgenic NOD mice expressing human CD20, to enable depletion using a human anti-CD20 monoclonal antibody. We evaluated the effect of depletion and repopulation on regulatory B cells, testing whether the protection afforded by B cell depletion was due to a change in regulatory B cell number or function. B cells with putative regulatory phenotypes were susceptible to depletion and, although the treatment with anti-CD20 reduced the incidence and delayed the onset of diabetes, there was no difference in the IL-10 producing B cell population by the time of full repopulation of B cells. Thus, this protective effect of B cell depletion was unlikely to be due to IL-10-producing B cells. In conclusion, for the first time, regulatory B cells were extensively studied in NOD mice and we demonstrated that protected NOD mice had higher frequencies of spleen B cells producing IL-10 than diabetic NOD mice. Further investigation is warranted to understand how these IL-10-producing B cells contribute to protection against type 1 diabetes

Review: Unravelling the role of DNA sensing in alum adjuvant activity

No abstract available

Is the BCG Vaccine Safe for Undernourished Individuals?

Cellular immunity is critical for protection against tuberculosis, but its integrity is compromised during undernutrition. The present study was designed to evaluate if the attenuated mycobacterium BCG is a safe vaccine for undernourished individuals. An experimental model of undernutrition was established by subjecting BALB/c mice to dietary restriction. These animals received 70% of the amount of food consumed by the healthy control group and exhibited physiological alterations compatible with malnutrition, including body weight loss, reduced levels of triglycerides and glucose, and reduced lymphocyte numbers. Undernourished mice were immunized with BCG, and the mycobacterial loads in lymph nodes, spleen, liver, lungs, and thymus were determined. A much higher proportion of undernourished mice exhibited bacterial dissemination to the lymph nodes, spleen and liver. In addition, only undernourished animals had bacteria in the lungs and thymus. Concomitant with higher mycobacterial loads and more widespread BCG dissemination in undernourished mice, production of TNF-α, IFN-γ, and IL-10 was also diminished in these mice. Taken together, these results indicate that BCG infection is more severe in undernourished mice. Whether a similar phenomenon exists in undernourished children or not remains to be thoroughly investigated

Is the BCG vaccine safe for undernourished individuals?

Cellular immunity is critical for protection against tuberculosis, but its integrity is compromised during undernutrition. The present study was designed to evaluate if the attenuated mycobacterium BCG is a safe vaccine for undernourished individuals. An experimental model of undernutrition was established by subjecting BALB/c mice to dietary restriction. These animals received 70% of the amount of food consumed by the healthy control group and exhibited physiological alterations compatible with malnutrition, including body weight loss, reduced levels of triglycerides and glucose, and reduced lymphocyte numbers. Undernourished mice were immunized with BCG, and the mycobacterial loads in lymph nodes, spleen, liver, lungs, and thymus were determined. A much higher proportion of undernourished mice exhibited bacterial dissemination to the lymph nodes, spleen and liver. In addition, only undernourished animals had bacteria in the lungs and thymus. Concomitant with higher mycobacterial loads and more widespread BCG dissemination in undernourished mice, production of TNF-α, IFN-γ, and IL-10 was also diminished in these mice. Taken together, these results indicate that BCG infection is more severe in undernourished mice. Whether a similar phenomenon exists in undernourished children or not remains to be thoroughly investigated

Is the BCG Vaccine Safe for Undernourished Individuals?

Cellular immunity is critical for protection against tuberculosis, but its integrity is compromised during undernutrition. The present study was designed to evaluate if the attenuated mycobacterium BCG is a safe vaccine for undernourished individuals. An experimental model of undernutrition was established by subjecting BALB/c mice to dietary restriction. These animals received 70% of the amount of food consumed by the healthy control group and exhibited physiological alterations compatible with malnutrition, including body weight loss, reduced levels of triglycerides and glucose, and reduced lymphocyte numbers. Undernourished mice were immunized with BCG, and the mycobacterial loads in lymph nodes, spleen, liver, lungs, and thymus were determined. A much higher proportion of undernourished mice exhibited bacterial dissemination to the lymph nodes, spleen and liver. In addition, only undernourished animals had bacteria in the lungs and thymus. Concomitant with higher mycobacterial loads and more widespread BCG dissemination in undernourished mice, production of TNF-α, IFN-γ, and IL-10 was also diminished in these mice. Taken together, these results indicate that BCG infection is more severe in undernourished mice. Whether a similar phenomenon exists in undernourished children or not remains to be thoroughly investigated

Commercial Bovine Proteoglycan Is Highly Arthritogenic and Can Be Used as an Alternative Antigen Source for PGIA Model

Rheumatoid arthritis (RA) is the most common systemic autoimmune disease. It affects mainly the joints, causing synovitis, cartilage destruction, and bone erosion. Many experimental models are used to study the mechanisms involved in immunopathogenesis and new therapies for this disease. Proteoglycan-induced arthritis (PGIA) is a widely used model based on the cross-reactivity of injected foreign (usually human) PG and mice self-PG. Considering the complexity of the extraction and purification of human PG, in this study we evaluated the arthritogenicity of bovine PG that is commercially available. Bovine PG was highly arthritogenic, triggering 100% incidence of arthritis in female BALB/c retired breeder mice. Animals immunized with bovine PG presented clinical symptoms and histopathological features similar to human RA and other experimental models. Moreover, bovine PG immunization determined higher levels of proinflammatory and anti-inflammatory cytokines in arthritic mice compared to healthy ones. As expected, only the arthritic group produced IgG1 and IgG2a antibodies against PG. Thus, commercial bovine PG can be used as an alternative antigenic source to PGIA for the study of many RA aspects, including the immunopathogenesis of the disease and also the development of new therapies

Persistent Inflammation in the CNS during Chronic EAE Despite Local Absence of IL-17 Production

Experimental autoimmune encephalomyelitis (EAE) is an artificially induced demyelination of the central nervous system (CNS) that resembles multiple sclerosis in its clinical, histopathological, and immunological features. Activated Th1 and Th17 cells are thought to be the main immunological players during EAE development. This study was designed to evaluate peripheral and local contribution of IL-17 to acute and chronic EAE stages. C57BL/6 mice were immunized with MOG plus complete Freund's adjuvant followed by pertussis toxin. Mice presented an initial acute phase characterized by accentuated weight loss and high clinical score, followed by a partial recovery when the animals reached normal body weight and smaller clinical scores. Spleen cells stimulated with MOG produced significantly higher levels of IFN-γ during the acute period whereas similar IL-17 levels were produced during both disease stages. CNS-infiltrating cells stimulated with MOG produced similar amounts of IFN-γ but, IL-17 was produced only at the acute phase of EAE. The percentage of Foxp3+ Treg cells, at the spleen and CNS, was elevated during both phases. The degree of inflammation was similar at both disease stages. Partial clinical recovery observed during chronic EAE was associated with no IL-17 production and presence of Foxp3+ Treg cells in the CNS

A EXTENSÃO UNIVERSITÁRIA E SUAS INTERFACES COM A FORMAÇÃO INICIAL EM EDUCAÇÃO FÍSICA

A extensão universitária compõe um dos tripés da Universidade, tendo o objetivo de atender às demandas da comunidade, aproximando os estudantes da realidade vivenciada na profissão. O objetivo do presente estudo foi identicar a percepção dos participantes quanto à qualidade dos projetos de extensão da ESEF/UFPel no que diz respeito à sua organização, satisfação dos participantes e suas interfaces com a formação dos estudantes. Foi realizada uma pesquisa exploratória e de caráter qualitativo, sendo selecionados randomicamente 50% dos projetos ativos na Pró-Reitoria de Extensão e Cultura (PREC) e vinculados à Escola Superior de Educação Física (ESEF/UFPel). As respostas foram separadas em dois grupos, comunidade geral (CG) e comunidade escolar (CE) e, no total, participaram 152 respondentes oriundos de nove projetos de extensão. Como principais resultados, detectou-se que, na maioria dos indicadores, os participantes consideraram que os projetos são qualificados e cumprem com o seu objetivo de atendimento à comunidade. No entanto, existem opiniões opostas entre os grupos em alguns dos indicadores, sobretudo oferta de vagas e divulgação de oportunidades. Foi possível concluir que, os projetos de extensão da ESEF/UFPel possuem e entregam bons níveis de satisfação nos quesitos de organização e participação, além de contribuir para a formação inicial e profissional dos alunos que participam

Revealing stromal and lymphoid sources of Col3a1-expression during inflammation using a novel reporter mouse

One of the earliest signs of dysregulation of the homeostatic process of fibrosis, associated with pathology in chronic conditions such as rheumatoid arthritis (RA), is the overexpression of collagen type III (COL-3). Critically, there is still relatively little known regarding the identity of the cell types expressing the gene encoding COL-3 (Col3a1). Identifying and characterising Col3a1-expressing cells during the development of fibrosis could reveal new targets for diagnosis and treatment of fibrosis-related pathologies. As such, a reporter mouse expressing concomitantly Col3a1 and mKate-2, a fluorescent protein, was generated. Using models of footpad inflammation, we demonstrated its effectiveness as a tool to measure the expression of COL-3 during the repair process and provided an initial characterisation of some of the stromal and immune cells responsible for Col3a1 expression

pVAXhsp65 vaccination primes for high IL-10 production and decreases experimental encephalomyelitis severity

Experimental autoimmune encephalomyelitis (EAE) is a demyelinating pathology of the central nervous system (CNS) used as a model to study multiple sclerosis immunopathology. EAE has also been extensively employed to evaluate potentially therapeutic schemes. Considering the presence of an immune response directed to heat shock proteins (hsps) in autoimmune diseases and the immunoregulatory potential of these molecules, we evaluated the effect of a previous immunization with a genetic vaccine containing the mycobacterial hsp65 gene on EAE development. C57BL/6 mice were immunized with 4 pVAXhsp65 doses and 14 days later were submitted to EAE induction by immunization with myelin oligodendrocyte glycoprotein (MOG35-55) emulsified in Complete Freund’s Adjuvant. Vaccinated mice presented significant lower clinical scores and lost less body weight. MOG35-55 immunization also determined less inflammation in lumbar spinal cord but did not change CD4+CD25+Foxp3+ T cells frequency in spleen and CNS. Infiltrating cells from the CNS stimulated with rhsp65 produced significantly higher levels of IL-10. These results suggest that the ability of pVAXhsp65 vaccination to control EAE development is associated with IL-10 induction