Gene expression profile of human T cells following a single stimulation of peripheral blood mononuclear cells with anti-CD3 antibodies
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 dis...
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| Format: | Article |
| Language: | English |
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BMC
2019-07-01
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| Series: | BMC Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s12864-019-5967-8 |
| _version_ | 1811220309276098560 |
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| author | Isabel Garcia Sousa Kelly Cristina Rodrigues Simi Manuela Maragno do Almo Maryani Andressa Gomes Bezerra Gero Doose Tainá Raiol Peter F. Stadler Steve Hoffmann Andréa Queiroz Maranhão Marcelo Macedo Brigido |
| author_facet | Isabel Garcia Sousa Kelly Cristina Rodrigues Simi Manuela Maragno do Almo Maryani Andressa Gomes Bezerra Gero Doose Tainá Raiol Peter F. Stadler Steve Hoffmann Andréa Queiroz Maranhão Marcelo Macedo Brigido |
| author_sort | Isabel Garcia Sousa |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T07:39:28Z |
| format | Article |
| id | doaj.art-ddc89d2e50b348ad8f38428d7c1ae7e5 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-04-12T07:39:28Z |
| publishDate | 2019-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-ddc89d2e50b348ad8f38428d7c1ae7e52022-12-22T03:41:51ZengBMCBMC Genomics1471-21642019-07-0120111410.1186/s12864-019-5967-8Gene expression profile of human T cells following a single stimulation of peripheral blood mononuclear cells with anti-CD3 antibodiesIsabel Garcia Sousa0Kelly Cristina Rodrigues Simi1Manuela Maragno do Almo2Maryani Andressa Gomes Bezerra3Gero Doose4Tainá Raiol5Peter F. Stadler6Steve Hoffmann7Andréa Queiroz Maranhão8Marcelo Macedo Brigido9Department of Cell Biology, Institute of Biological Sciences, University of BrasiliaMolecular Biology Graduation Program, Institute of Biological Sciences, University of BrasiliaMolecular Pathology Graduation Program, Medicine Faculty, University of BrasiliaMolecular Biology Graduation Program, Institute of Biological Sciences, University of BrasiliaBioinformatics Group, Department of Computer Science and Interdisciplinary Center of Bioinformatics, University of LeipzigFiocruz Brasilia, Oswaldo Cruz Foundation (GEREB/Fiocruz)Bioinformatics Group, Department of Computer Science and Interdisciplinary Center of Bioinformatics, University of LeipzigBioinformatics Group, Department of Computer Science and Interdisciplinary Center of Bioinformatics, University of LeipzigDepartment of Cell Biology, Institute of Biological Sciences, University of BrasiliaDepartment of Cell Biology, Institute of Biological Sciences, University of BrasiliaAbstract 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.http://link.springer.com/article/10.1186/s12864-019-5967-8Anti-CD3RNA-seqAntibody therapyRegulatory T cellsAntibody engineering |
| spellingShingle | Isabel Garcia Sousa Kelly Cristina Rodrigues Simi Manuela Maragno do Almo Maryani Andressa Gomes Bezerra Gero Doose Tainá Raiol Peter F. Stadler Steve Hoffmann Andréa Queiroz Maranhão Marcelo Macedo Brigido Gene expression profile of human T cells following a single stimulation of peripheral blood mononuclear cells with anti-CD3 antibodies BMC Genomics Anti-CD3 RNA-seq Antibody therapy Regulatory T cells Antibody engineering |
| title | Gene expression profile of human T cells following a single stimulation of peripheral blood mononuclear cells with anti-CD3 antibodies |
| title_full | Gene expression profile of human T cells following a single stimulation of peripheral blood mononuclear cells with anti-CD3 antibodies |
| title_fullStr | Gene expression profile of human T cells following a single stimulation of peripheral blood mononuclear cells with anti-CD3 antibodies |
| title_full_unstemmed | Gene expression profile of human T cells following a single stimulation of peripheral blood mononuclear cells with anti-CD3 antibodies |
| title_short | Gene expression profile of human T cells following a single stimulation of peripheral blood mononuclear cells with anti-CD3 antibodies |
| title_sort | gene expression profile of human t cells following a single stimulation of peripheral blood mononuclear cells with anti cd3 antibodies |
| topic | Anti-CD3 RNA-seq Antibody therapy Regulatory T cells Antibody engineering |
| url | http://link.springer.com/article/10.1186/s12864-019-5967-8 |
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