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https://www.arca.fiocruz.br/handle/icict/42676
GENE EXPRESSION PROFILE OF HUMAN T CELLS FOLLOWING A SINGLE STIMULATION OF PERIPHERAL BLOOD MONONUCLEAR CELLS WITH ANTI-CD3 ANTIBODIES
Complexo CD3
Ontologia Genética
Marcadores Genéticos
Fenótipo
Linfócitos T
Perfilação da Expressão Gênica
Author
Affilliation
University of Brasilia. Institute of Biological Sciences. Department of Cell Biology. Brasilia, DF, Brazil / Instituto Nacional de Ciências e Tecnologia. Instituto de Investigação em Imunologia. Brasilia, DF, Brazil.
University of Brasilia. Institute of Biological Sciences. Molecular Biology Graduation Program. Brasilia, DF, Brazil.
University of Brasilia. Medicine Faculty. Molecular Pathology Graduation Program. Brasilia, DF, Brazil.
University of Brasilia. Institute of Biological Sciences. Molecular Biology Graduation Program. Brasilia, DF, Brazil.
University of Leipzig. Department of Computer Science and Interdisciplinary Center of Bioinformatics. Bioinformatics Group. Leipzig, Germany / University of Leipzig. Interdisciplinary Center for Bioinformatics. Leipzig, Germany.
Fundação Oswaldo Cruz. Fiocruz Brasília. Brasília, DF, Brasil.
University of Leipzig. Department of Computer Science and Interdisciplinary Center of Bioinformatics. Bioinformatics Group. Leipzig, Germany / Max-Planck-Institute for Mathematics in the Sciences. Leipzig, Germany / Santa Fe Institute. Santa Fe, NM, USA.
University of Leipzig. Department of Computer Science and Interdisciplinary Center of Bioinformatics. Bioinformatics Group. Leipzig, Germany / Leibniz Institute on Ageing – Fritz Lipmann Institute (FLI) and Friedrich-Schiller-University Jena. Computational Biology Group. Jena, Germany.
University of Brasilia. Institute of Biological Sciences. Department of Cell Biology. Brasilia, DF, Brazil / Instituto Nacional de Ciências e Tecnologia. Instituto de Investigação em Imunologia. Brasilia, DF, Brazil.
University of Brasilia. Institute of Biological Sciences. Department of Cell Biology. Brasilia, DF, Brazil / Instituto Nacional de Ciências e Tecnologia. Instituto de Investigação em Imunologia. Brasilia, DF, Brazil.
University of Brasilia. Institute of Biological Sciences. Molecular Biology Graduation Program. Brasilia, DF, Brazil.
University of Brasilia. Medicine Faculty. Molecular Pathology Graduation Program. Brasilia, DF, Brazil.
University of Brasilia. Institute of Biological Sciences. Molecular Biology Graduation Program. Brasilia, DF, Brazil.
University of Leipzig. Department of Computer Science and Interdisciplinary Center of Bioinformatics. Bioinformatics Group. Leipzig, Germany / University of Leipzig. Interdisciplinary Center for Bioinformatics. Leipzig, Germany.
Fundação Oswaldo Cruz. Fiocruz Brasília. Brasília, DF, Brasil.
University of Leipzig. Department of Computer Science and Interdisciplinary Center of Bioinformatics. Bioinformatics Group. Leipzig, Germany / Max-Planck-Institute for Mathematics in the Sciences. Leipzig, Germany / Santa Fe Institute. Santa Fe, NM, USA.
University of Leipzig. Department of Computer Science and Interdisciplinary Center of Bioinformatics. Bioinformatics Group. Leipzig, Germany / Leibniz Institute on Ageing – Fritz Lipmann Institute (FLI) and Friedrich-Schiller-University Jena. Computational Biology Group. Jena, Germany.
University of Brasilia. Institute of Biological Sciences. Department of Cell Biology. Brasilia, DF, Brazil / Instituto Nacional de Ciências e Tecnologia. Instituto de Investigação em Imunologia. Brasilia, DF, Brazil.
University of Brasilia. Institute of Biological Sciences. Department of Cell Biology. Brasilia, DF, Brazil / Instituto Nacional de Ciências e Tecnologia. Instituto de Investigação em Imunologia. Brasilia, DF, Brazil.
Abstract
Anti-CD3 immunotherapy was initially approved for clinical use for renal transplantation rejection prevention. Subsequently, new generations of anti-CD3 antibodies have entered clinical trials for a broader spectrum of therapeutic applications, including cancer and autoimmune diseases. Despite their extensive use, little is known about the exact mechanism of these molecules, except that they are able to activate T cells, inducing an overall immunoregulatory and tolerogenic behavior. To better understand the effects of anti-CD3 antibodies on human T cells, PBMCs were stimulated, and then, we performed RNA-seq assays of enriched T cells to assess changes in their gene expression profiles. In this study, three different anti-CD3 antibodies were used for the stimulation: two recombinant antibody fragments, namely, a humanized and a chimeric FvFc molecule, and the prototype mouse mAb OKT3. Results: Gene Ontology categories and individual immunoregulatory markers were compared, suggesting a
similarity in modulated gene sets, mainly those for immunoregulatory and inflammatory terms. Upregulation of interleukin receptors, such as IL2RA, IL1R, IL12RB2, IL18R1, IL21R and IL23R, and of inhibitory molecules, such as FOXP3, CTLA4, TNFRSF18, LAG3 and PDCD1, were also observed, suggesting an inhibitory and exhausted phenotype. Conclusions: We used a deep transcriptome sequencing method for comparing three anti-CD3 antibodies in terms of Gene Ontology enrichment and immunological marker expression. The present data showed that both recombinant antibodies induced a compatible expression profile, suggesting that they might be candidates for a closer evaluation with respect to their therapeutic value. Moreover, the proposed methodology is amenable to be more generally applied for molecular comparison of cell receptor dependent antibody therapy.
DeCS
Anticorpos MonoclonaisComplexo CD3
Ontologia Genética
Marcadores Genéticos
Fenótipo
Linfócitos T
Perfilação da Expressão Gênica
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