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The benefits attributed to mesenchymal stem/stromal cells (MSC) in cell therapy applications are mainly attributed to the secretion of factors, which exhibit immunomodulatory and anti-inflammatory effects and stimulate angiogenesis. Despite the desirable features such as high proliferation levels, multipotency, and immune response regulation, there are important variables that must be considered. Although presenting similar morphological aspects, MSC collected from different tissues can form heterogeneous cellular populations and, therefore, manifest functional differences. Thus, the source of MSC should be a factor to be considered in the development of novel therapies. The following text presents an updated review of recent research outcomes related to Wharton’s jelly mesenchymal stem/stromal cells (WJ-MSC), harvested from umbilical cords and considered novel and potential candidates for the development of cell-based approaches. This text highlights information on how WJ-MSC affect immune responses in comparison with other sources of MSC.

Systemic Autoimmune Diseases, a group of chronic inflammatory conditions, have variable symptoms and difficult diagnosis. In order to reclassify them based on genetic markers rather than clinical criteria, we performed clustering of Single Nucleotide Polymorphisms. However naive approaches tend to group patients primarily by their geographic origin. To reduce this “ancestry signal”, we developed SNPClust, a method to select large sources of ancestry-independent genetic variations from all variations detected by Principal Component Analysis. Applied to a Systemic Lupus Erythematosus case control dataset, SNPClust successfully reduced the ancestry signal. Results were compared with association studies between the cases and controls without or with reference population stratification correction methods. SNPClust amplified the disease discriminating signal and the ratio of significant associations outside the HLA locus was greater compared to population stratification correction methods. SNPClust will enable the use of ancestry-independent genetic information in the reclassification of Systemic Autoimmune Diseases. SNPClust is available as an R package and demonstrated on the public Human Genome Diversity Project dataset at https://github.com/ThomasChln/snpclust., Funding: Quartz Bio S.A. provided support in the form of salaries for TC, ADC, and JW, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work has received support from the EU/EFPIA/ Innovative Medicines Initiative Joint Undertaking PRECISESADS grant no. 115565

The second part of this review deals with the molecules and processes involved in the processing and presentation of the antigenic fragments to the T-cell receptor. Though the nature of the antigens presented varies, the most significant class of antigens is proteins, processed within the cell to be then recognized in the form of peptides, a mechanism that confers an extraordinary degree of precision to this mode of immune response. The efficiency and accuracy of this system is also the result of the myriad of mechanisms involved in the processing of proteins and production of peptides, in addition to the capture and recycling of alternative sources aiming to generate further diversity in the presentation to T-cells. A segunda parte desta revisão trata das moléculas e processos envolvidos no processamento e apresentação dos fragmentos antigênicos ao receptor de célula-T. Apesar de variar a natureza do antígeno apresentado, a classe mais significativa é a das proteínas, as quais são processadas dentro da célula para enfim serem reconhecidas na forma de peptídeos, o que confere um grau extraordinário de precisão a essa forma de resposta imune. A eficiência e a precisão desse sistema se devem também à miríade de mecanismos envolvidos no processamento de proteínas e produção de peptídeos, além da captura e reciclagem de fontes alternativas de antígenos com o objetivo de gerar ainda maior diversidade na apresentação à célula-T.

Trabalho completo: acesso restrito, p. 204–212 Submitted by Bruna Lessa (lessbruna@gmail.com) on 2012-08-20T19:09:29Z No. of bitstreams: 1 (172).pdf: 354283 bytes, checksum: 782806db1c3215c834afd72dc34157d5 (MD5) Made available in DSpace on 2012-08-20T19:09:29Z (GMT). No. of bitstreams: 1 (172).pdf: 354283 bytes, checksum: 782806db1c3215c834afd72dc34157d5 (MD5) Previous issue date: 2005-02 he development of a defined anti-schistosomiasis vaccine would contribute to the current control strategy mainly because immunization provides long-lasting immunity to the disease. Sm14, one of the six Schistosoma mansoni antigens selected by WHO as a candidate to compose a subunit vaccine against schistosomiasis, has been associated with resistance to S. mansoni infection in human beings and is able to induce protection in the murine model. To identify human T cell epitopes in Sm14, we used the TEPITOPE algorithm to select peptides that would most likely bind to several HLA-DR molecules. In this study, three Sm14 epitopes were selected and produced as synthetic peptides. Human T cell responses from schistosomiasis patients living in endemic areas in Brazil were determined by proliferation assay and IL-5 and IFN-γ measurements. Differential peptide recognition and cytokine production in response to Sm14 epitopes were observed in individuals resistant to S. mansoni infection versus susceptible individuals. Sm14(32-48) and Sm14(53-69) peptides were preferentially recognized by peripheral blood mononuclear cells (PBMCs) of S. mansoni-resistant individuals, and Sm14(53-69) induced significant production of IFN-γ. Additionally, Sm14(32-48) and Sm14(53-69) were “promiscuous” peptides, since they were able to induce cellular immune responses in individuals carrying 10 and 8, respectively, of the 11 HLA-DR molecules expressed in the studied population. Among Sm14 synthetic peptides tested in this study, we identified Sm14(32-48) and Sm14(53-69) as promising candidates to compose an anti-schistosomiasis vaccine, since they seem to be related to resistance to human schistosomiasis.