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OBJECTIVE Characterization of partial remission using the insulin dose-adjusted HbA1c (IDAA1c) ≤ 9 definition in a multiethnic Brazilian population of children and adolescents with type 1 diabetes (T1D), in addition with the determination of both Class II HLA genotype and autoantibodies. METHODS We analyzed the prevalence of partial remission in 51 new-onset T1D patients with a median time follow-up of 13 months from diagnosis. For this study, anti-GAD65, anti-IA2 and HLA class II genotyping were considered. RESULTS Partial remission occurred in 41.2% of T1D patients until 3 months after diagnosis, mainly in those aged 5-15 years. We have demonstrated a significant increase in the haplotypes of class II HLA DRB1*0301-DQB1*0201 in children and adolescents with a partial remission phase of the disease (42.9% vs 21.7% in non-remitters, P = .0291). This haplotype was also associated with the reduction of anti-IA2 antibodies production. Homozygote DRB1*03-DQB1*0201/DRB1*03-DQB1*0201 children had the lowest prevalence of IA-2A antibodies (P = .0402). However, this association does not correlate with the time of the remission phase. CONCLUSION Although the number of patients studied was reduced, our data suggested that the association between genetics and decrease in antibody production to certain islet auto-antigen may contribute, at least in part, to the remission phase of T1D.

The current study was aimed to evaluate the occurrence of Staphylococcus in institutional and domestic kitchens, as well as in meals served at child care centers and as desserts in local restaurants of Campinas, Brazil. Recovered isolates were analyzed by qPCR for Staphylococcal Enterotoxin (SE) expression and results compared to the traditional SE detection assay by immunoassay. Six different points (sink, refrigerator handle, stove burner knob, cutting board, cutting knives and dishcloth), were assessed in kitchens of 4 child care centers and 10 domestic kitchens. In addition, the hands and nostrils of the kitchen personnel were sampled. Meals served at the childcare centers (8 chicken meat and 8 chayotes) and desserts containing pastry cream from 10 restaurants were examined for the presence and levels present of Staphylococcus spp. Samples were collected during two distinct periods, and between them (1 month), a lecture regarding “Good practices in food handling” was given to all staff by the authors. Three hundred and twenty colonies (n = 320), typical and atypical belonging to Staphylococcus were recovered from all sampling points. Among 320 recovered colonies, fifty isolates were confirmed as Staphylococcus species (n = 47 from environmental samples and n = 3 from food samples). Also, S. aureus was responsible for the plurality of identified isolates (30%). The highest count for Staphylococcus was measured as 4.52 log10 CFU/50 cm2 on the door handle of a refrigerator. Twelve percent of all tested strains (n = 50) likely expressed enterotoxins, and Staphylococcal Enterotoxin D (SED) was the SE most often (3 out of 6; or 50%) identified. The findings of the current study can be used is establishing guidelines for the improvement of cleanliness and food handling practices in the kitchens of Campinas, Brazil. Ultimately, reducing the occurrence of foodborne disease outbreaks and increased public health.

A Esclerose Múltipla é uma doença autoimune crônica e desmielinizante, que envolte fatores genéticos e ambientais. Acredita-se que dentre esses fatores está a deficiência de Vitamina D3. Anteriormente, nós demonstramos que as células dendríticas (DCs) são o principal alvo de regulação da vitamina, induzindo um perfil tolerogênico das DCs dependente da expressão de IDO. Essas DCs IDO+ induzem o aumento e a estimulação de linfócitos T CD4+FOXP3+ com ação reguladora, diminuido a resposta inflamatória no modelo experimental (EAE). A IDO gera quinureninas, que serão reconhecidas pelo receptor aril hidrocarboneto (AhR) gerando uma resposta imunossupressora. Assim, nosso objetivo foi verificar a participação dos produtos da IDO expressa por células dendríticas tolerogênicas, geradas na presença da vitamina D3, na indução de células T regulatórias.

A esclerose multipla é uma doença desmielinizante do sistema nervoso central. Atualmente, o modelo animal mais aceito para estuda-la é a encefalomielite experimental autoimune (EAE) induzida em camundongos. Nosso objetivo neste estudo foi estudar a regulação gênica de IL17 e IFNY durante a evolução desta doença, já que dados preliminares demonstraram que tal doença é mediada por linfócitos Th1e/ou Th17 que acabam por adquirir carácter citotóxico no SNC.

It has been demonstrated the cytotoxic activity of TCD4+ encaphalitogenic lymphocytes and it's crucial role in the development of Experimental Autoimmune Encephalomyelitis (EAE). Furthermore, our laboratory has seen a switch from Th17 profile to Th1-like during the evolution of EAE. Thus, these lymphocytes decreased IL-17A production while begin to produce IFNγ when infiltrate the central nervous system. Therefore, our goal was to verify the mechanisms that governs the convertion of Th17 cells into IFNγ-producing cells.

Background Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease that affects young adults. It is characterized by generating a chronic demyelinating autoimmune inflammation in the central nervous system. An experimental model for studying MS is the experimental autoimmune encephalomyelitis (EAE), induced by immunization with antigenic proteins from myelin. Aims The present study investigated the evolution of EAE in pregabalin treated animals up to the remission phase. Methods and results The results demonstrated a delay in the onset of the disease with statistical differences at the 10th and the 16th day after immunization. Additionally, the walking track test (CatWalk) was used to evaluate different parameters related to motor function. Although no difference between groups was obtained for the foot print pressure, the regularity index was improved post treatment, indicating a better motor coordination. The immunohistochemical analysis of putative synapse preservation and glial reactivity revealed that pregabalin treatment improved the overall morphology of the spinal cord. A preservation of circuits was depicted and the glial reaction was downregulated during the course of the disease. qRT-PCR data did not show immunomodulatory effects of pregabalin, indicating that the positive effects were restricted to the CNS environment. Conclusions Overall, the present data indicate that pregabalin is efficient for reducing the seriousness of EAE, delaying its course as well as reducing synaptic loss and astroglial reaction.

Multiple sclerosis, which is the most common cause of chronic neurological disability in young adults, is an inflammatory, demyelinating, and neurodegenerative disease of the CNS, which leads to the formation of multiple foci of demyelinated lesions in the white matter. The diagnosis is based currently on magnetic resonance image and evidence of dissemination in time and space. However, this could be facilitated if biomarkers were available to rule out other disorders with similar symptoms as well as to avoid cerebrospinal fluid analysis, which requires an invasive collection. Additionally, the molecular mechanisms of the disease are not completely elucidated, especially those related to the neurodegenerative aspects of the disease. The identification of biomarker candidates and molecular mechanisms of multiple sclerosis may be approached by proteomics. In the last 10 years, proteomic techniques have been applied in different biological samples (CNS tissue, cerebrospinal fluid, and blood) from multiple sclerosis patients and in its experimental model. In this review, we summarize these data, presenting their value to the current knowledge of the disease mechanisms, as well as their importance in identifying biomarkers or treatment targets.

Despite the evolution of treatments in the past decade, acute inflammatory autoimmune diseases of the peripheral nervous system are still a concern due to their considerable morbidity and mortality [1]. Guillain-Barr e syndrome (GBS) is an acute inflammatory disorder. The study of experimental autoimmune neuritis (EAN), the experimental model of GBS, has provided most of the knowledge regarding GBS disease mechanisms. Inflammatory lesions are primarily located in the sciatic nerves and the cauda equina of EAN-affected Lewis rats [2]. Lesions are characterized by an accumulation of inflammatory cells, primarily T cells, and macrophages. The inflammatory response during EAN is characterized mainly by the migration of neuritogenic cells into the peripheral nerves and by the production and secretion of proinflammatory cytokines, such as IFNc, TNFa, IL-6, and IL-17 [3]. During the last years, hematopoietic factors, such as erythropoietin, granulocyte–macrophage colony-stimulating factor and granulocyte–colony-stimulating factor (G-CSF), have been successfully used to modify experimental autoimmune diseases [4,5]. Moreover, G-CSF has an important and strong tolerogenic function. This cytokine recruits immature dendritic cells (DCs), which induce tolerance through the enhancement of regulatory T cells [5]. In this study, we investigated the effects of short-term G-CSF treatment on the evolution of EAN. EAN was induced using the neuritogenic peptide P253-78 as previously described [6]. The clinical signs of EAN were significantly reduced by the in vivo administration of G-CSF in a short-term treatment regimen (Figure 1A). The development of EAN is characterized by the sensitization and activation of neuritogenic T cells in the peripheral immune organs. These cells migrate into peripheral nerves and release inflammatory mediators, which may contribute directly or indirectly to the destruction of the myelin sheath. We observed a significant reduction in the specific proliferative response of T cells from Lewis rats with EAN treated with G-CSF compared with the cells from the control animals (Figure 1B). Moreover, G-CSF treatment reduced the mononuclear cell infiltration into the sciatic nerve (Figure 1C). The EAN autoaggressive response is characterized by the expression and release of Th1 and/or Th17 cytokines. Therefore, we evaluated the expression, by real-time PCR (Figure S1), of Th1 and Th17 cytokines and transcription factors, in the lymph nodes 10 days after immunization, prior to the migration of the neuritogenic cells from the periphery to the target tissue. We observed a consistent downregulation in the expression of the Th1 (T-bet) and Th17 (RORa and RORct) transcription factors in the G-CSFtreated group compared with control group (Figure 1D). Corroborating the changes in the transcription factors expression profile, the expression of proinflammatory cytokines (IFNc, IL-17A, IL17E, and IL-6) was reduced in the G-CSF-treated group compared with the control group. G-CSF treatment also led to an increase in the expression of anti-inflammatory cytokines, such as IL-10 and

The induction of autoimmune encephalomyelitis (EAE) in Lewis rats results in a period of exacerbation followed by complete recovery. Therefore, this model is widely used for studying the evolution of multiple sclerosis. In the present investigation, differentially expressed proteins in the spinal cord of Lewis rats during the evolution of EAE were assessed using the combination of 2DE and MALDI-TOF MS. The majority of the differentially expressed proteins were identified during the acute phase of EAE, in relation to naïve control animals. On the other hand, recovered rats presented a similar protein expression pattern in comparison with the naïve ones. This observation can be explained, at least in part, by the intense catabolism existent in acute phase due to nervous tissue damage. In recovered rats, we have described the upregulation of proteins that are apparently involved in the recovery of damaged tissue, such as light and medium neurofilaments, glial fibrillary acidic protein, tubulins subunits, and quaking protein. These proteins are involved mainly in cell growth, myelination, and remyelination as well as in astrocyte and oligodendrocyte maturation. The present study has demonstrated that the inflammatory response, characterized by an increase of the proliferative response and infiltration of autoreactive T lymphocytes in the central nervous system, occurs simultaneously with neurodegeneration.

The present study investigates the effects of xenotransplantation of Adipose Tissue Mesenchymal Stem Cells (AT-MSCs) in animals after ventral root avulsion. AT-MSC has similar characteristics to bone marrow mesenchymal stem cells (BM-MSCs), such as immunomodulatory properties and expression of neurotrophic factors. In this study, Lewis rats were submitted to surgery for unilateral avulsion of the lumbar ventral roots and received 5 × 105 AT-MSCs via the lateral funiculus. Two weeks after cell administration, the animals were sacrificed and the moto neurons, T lymphocytes and cell defense nervous system were analyzed. An increased neuronal survival and partial preservation of synaptophysin-positive nerve terminals, related to GDNF and BDNF expression of AT-MSCs and reduction of pro-inflammatory reaction were observed. In conclusion, AT-MSCs prevent second phase neuronal injury, since they suppressed lymphocyte, astroglia and microglia effects, which finally contributed to rat motor-neuron survival and synaptic stability of the lesioned motor-neuron. Moreover, the survival of the injected AT- MSCs lasted for at least 14 days. These results indicate that neuronal survival after lesion, followed by mesenchymal stem cell (MSC) administration, might occur through cytokine release and immunomodulation, thus suggesting that AT-MSCs are promising cells for the therapy of neuronal lesions.

BACKGROUND: A growing body of evidence supports the hypothesis that vitamin D is an important environmental factor in the etiology of T‐cell‐mediated autoimmune diseases such as multiple sclerosis (MS). AIM: The purpose of this study was exploring the mechanisms underlying the beneficial effect of vitamin D3 in encephalomyelitis (EAE). METHODS: We treated monophasic experimental autoimmune EAE, induced in Lewis rat, with vitamin D3 and adoptively transfer tolerogenic bone marrow‐derived DCs generated in the presence of vitamin D3. RESULTS: This study provides evidence that the in vivo administration of vitamin D(3,) as well as the adoptive transfer of vitamin D(3)‐induced IDO (+) immature/tolerogenic dendritic cells, leads to a significant increase in the percentage of CD4(+) CD25(+)Foxp3(+) regulatory T cells in the lymph nodes in a rat model of MS, experimental autoimmune EAE. Concomitant with the increase in this cell population, there is a significant decrease in the number of autoreactive T cells in the central nervous system. Bone marrow‐derived DCs cultivated in the presence of vitamin D(3) present a tolerogenic profile with high IL‐10, TNFα, and IDO expression and decreased MHC‐II and CD80 expression. The adoptive transfer of IDO (+) DCs induces a significant increase in the percentage of CD4(+) CD25(+)Foxp3(+) T cells in the lymph nodes, comparable with vitamin D(3) treatment. CONCLUSION: These mechanisms contribute actively to the generation of a microenvironment in the lymph nodes that suppresses the activation of encephalitogenic T cells, resulting in the downregulation of the inflammatory response in the central nervous system.

Our data demonstrate that multi-walled carbon nanotubes (MWCNTs) are internalized by macrophages, subsequently activating them to produce interleukin (IL)-12 (IL-12). This cytokine induced the proliferative response of T lymphocytes to a nonspecific mitogen and to ovalbumin (OVA). This increase in the proliferative response was accompanied by an increase in the expression of pro-inflammatory cytokines, such as interferon-gamma (IFNγ), tumor necrosis factor-alpha (TNFα) and IL-6, in mice inoculated with MWCNTs, whether or not they had been immunized with OVA. A decrease in the expression of transforming growth factor-beta (TGFβ) was observed in the mice treated with MWCNTs, whereas the suppression of the expression of both TGFβ and IL-10 was observed in mice that had been both treated and immunized. The activation of the T lymphocyte response by the pro-inflammatory cytokines leads to an increase in antibody production to OVA, suggesting the important immunostimulatory effect of carbon nanotubes.

The plasmacytoid dendritic cells (pDCs) express a high level of Toll-like receptor 9 (TLR-9), which recognizes viral DNA. Activated via TLR-9, pDCs also secrete large amounts of type I interferon which are involved either in stimulation or down regulation of immune response in multiple sclerosis (MS). In the present study, we determinate pDCs levels by flow cytometry in Cerebrospinal Fluid (CSF) and Peripheral Blood from MS patients in relapsing and in remitting phases of the disease, comparing with other non-inflammatory diseases (OND). We provide evidence that MS patients in relapse without any treatment have a significantly (p < 0.01) higher percentage of pDCs in CSF than do patients in remission or those with OND. No change in the percentage of pDCs was observed in the peripheral blood of any of these patients. The increase of pDCs in central nervous system during relapse may be explained either by a virus infection or a down regulatory process.

Background Experimental autoimmune encephalomyelitis (EAE) is used as an animal model for human multiple sclerosis (MS), which is an inflammatory demyelinating autoimmune disease of the central nervous system characterized by activation of Th1 and/or Th17 cells. Human autoimmune diseases can be either exacerbated or suppressed by infectious agents. Recent studies have shown that regulatory T cells play a crucial role in the escape mechanism of Plasmodium spp. both in humans and in experimental models. These cells suppress the Th1 response against the parasite and prevent its elimination. Regulatory T cells have been largely associated with protection or amelioration in several autoimmune diseases, mainly by their capacity to suppress proinflammatory response. Methodology/Principal Findings In this study, we verified that CD4+CD25+ regulatory T cells (T regs) generated during malaria infection (6 days after EAE induction) interfere with the evolution of EAE. We observed a positive correlation between the reduction of EAE clinical symptoms and an increase of parasitemia levels. Suppression of the disease was also accompanied by a decrease in the expression of IL-17 and IFN-γ and increases in the expression of IL-10 and TGF-β1 relative to EAE control mice. The adoptive transfer of CD4+CD25+ cells from P. chabaudi-infected mice reduced the clinical evolution of EAE, confirming the role of these T regs. Conclusions/Significance These data corroborate previous findings showing that infections interfere with the prevalence and evolution of autoimmune diseases by inducing regulatory T cells, which regulate EAE in an apparently non-specific manner.

Results Histological data confirmed that the non-functionalized MWCTN had been absorbed and kept retained into the phagocytes of the peri-pancreatic lymph nodes, spleen and liver, causing a granulomatous inflammatory response. Even though no differences were found in the frequency of the development of clinical diabetes or in the morphological characteristics of the pancreatic insulitis, female NOD mice treated with MWCTN presented a significant higher fluctuation of the average glycaemia compared to the control group during the entire study (p

Background Human type 1A diabetes (T1AD) has a broad spectrum of clinical presentations, which may be associated with the severity of autoimmune response and consequently, different levels of pancreatic beta cells destruction. The T1AD presents a partial remission phase. The remission phase is classically a short period in childhood-onset diabetes, but longer periods may occur especially in young.