Título:	Gene expression profile of human T cells following a single stimulation of peripheral blood mononuclear cells with anti-CD3 antibodies
Autor(es):	Sousa, Isabel Garcia Simi, Kelly Cristina Rodrigues Almo, Manuela Maragno do Bezerra, Maryani Andressa Gomes Doose, Gero Raiol, Tainá Stadler, Peter Florian Hoffmann, Steve Maranhão, Andréa Queiroz Brigido, Marcelo Macedo
E-mail do autor:	mailto:brigido@unb.br
ORCID:	https://orcid.org/0000-0002-7136-7059
Assunto:	Células T ANTI-CD3 Anticorpos monoclonais
Data de publicação:	2019
Editora:	Springer Nature
Referência:	SOUSA, Isabel Garcia et. al. Gene expression profile of human T cells following a single stimulation of peripheral blood mononuclear cells with anti-CD3 antibodies. BMC Genomics, v. 20, art. 593, 2019. DOI 10.1186/s12864-019-5967-8. Disponível em: https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-019-5967-8. Acesso em: 05 dez. 2022.
Abstract:	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.
Licença:	Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Fonte: https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-019-5967-8#rightslink. Acesso em: 05 dez. 2022.
DOI:	https://doi.org/10.1186/s12864-019-5967-8
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