Gene expression profile of human T cells following a single stimulation of peripheral blood mononuclear cells with anti-CD3 antibodies.

Autor: Sousa IG; Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil.; Instituto de Investigação em Imunologia, Instituto Nacional de Ciências e Tecnologia (iii-INCT), Brasilia, Brazil., Simi KCR; Molecular Biology Graduation Program, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil., do Almo MM; Molecular Pathology Graduation Program, Medicine Faculty, University of Brasilia, Brasilia, Brazil., Bezerra MAG; Molecular Biology Graduation Program, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil., Doose G; Bioinformatics Group, Department of Computer Science and Interdisciplinary Center of Bioinformatics, University of Leipzig, Leipzig, Germany.; Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany., Raiol T; Fiocruz Brasilia, Oswaldo Cruz Foundation (GEREB/Fiocruz), Brasilia, Brazil., Stadler PF; Bioinformatics Group, Department of Computer Science and Interdisciplinary Center of Bioinformatics, University of Leipzig, Leipzig, Germany.; Max-Planck-Institute for Mathematics in the Sciences, Leipzig, Germany.; Santa Fe Institute, Santa Fe, NM, USA., Hoffmann S; Bioinformatics Group, Department of Computer Science and Interdisciplinary Center of Bioinformatics, University of Leipzig, Leipzig, Germany.; Computational Biology Group, Leibniz Institute on Ageing - Fritz Lipmann Institute (FLI) and Friedrich-Schiller-University Jena, Jena, Germany., Maranhão AQ; Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil.; Instituto de Investigação em Imunologia, Instituto Nacional de Ciências e Tecnologia (iii-INCT), Brasilia, Brazil., Brigido MM; Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil. brigido@unb.br.; Instituto de Investigação em Imunologia, Instituto Nacional de Ciências e Tecnologia (iii-INCT), Brasilia, Brazil. brigido@unb.br.
Jazyk: angličtina
Zdroj: BMC genomics [BMC Genomics] 2019 Jul 19; Vol. 20 (1), pp. 593. Date of Electronic Publication: 2019 Jul 19.
DOI: 10.1186/s12864-019-5967-8
Abstrakt: Background: 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.
Databáze: MEDLINE
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