CD4+ and CD8+ regulatory T cell characterization in the rat using a unique transgenic Foxp3-EGFP model
Abstract Background Regulatory T cells (Treg) in diverse species include CD4+ and CD8+ T cells. In all species, CD8+ Treg have been only partially characterized and there is no rat model in which CD4+ and CD8+ FOXP3+ Treg are genetically tagged. Results We generated a Foxp3-EGFP rat transgenic line...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-01-01
|
| Series: | BMC Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12915-022-01502-0 |
| _version_ | 1797952363665817600 |
|---|---|
| author | Séverine Ménoret Laurent Tesson Séverine Remy Victor Gourain Céline Sérazin Claire Usal Aude Guiffes Vanessa Chenouard Laure-Hélène Ouisse Malika Gantier Jean-Marie Heslan Cynthia Fourgeux Jeremie Poschmann Carole Guillonneau Ignacio Anegon |
| author_facet | Séverine Ménoret Laurent Tesson Séverine Remy Victor Gourain Céline Sérazin Claire Usal Aude Guiffes Vanessa Chenouard Laure-Hélène Ouisse Malika Gantier Jean-Marie Heslan Cynthia Fourgeux Jeremie Poschmann Carole Guillonneau Ignacio Anegon |
| author_sort | Séverine Ménoret |
| collection | DOAJ |
| description | Abstract Background Regulatory T cells (Treg) in diverse species include CD4+ and CD8+ T cells. In all species, CD8+ Treg have been only partially characterized and there is no rat model in which CD4+ and CD8+ FOXP3+ Treg are genetically tagged. Results We generated a Foxp3-EGFP rat transgenic line in which FOXP3 gene was expressed and controlled EGFP. CD4+ and CD8+ T cells were the only cells that expressed EGFP, in similar proportion as observed with anti-FOXP3 antibodies and co-labeled in the same cells. CD4+EGFP+ Treg were 5–10 times more frequent than CD8+EGFP+ Treg. The suppressive activity of CD4+ and CD8+ Treg was largely confined to EGFP+ cells. RNAseq analyses showed similarities but also differences among CD4+ and CD8+ EGFP+ cells and provided the first description of the natural FOXP3+CD8+ Treg transcriptome. In vitro culture of CD4+ and CD8+ EGFP− cells with TGFbeta and IL-2 generated induced EGFP+ Treg. CD4+ and CD8+ EGFP+ Treg were expanded upon in vivo administration of a low dose of IL-2. Conclusions This new and unique rat line constitutes a useful model to identify and isolate viable CD4+ and CD8+ FOXP3+ Treg. Additionally, it allows to identify molecules expressed in CD8+ Treg that may allow to better define their phenotype and function not only in rats but also in other species. |
| first_indexed | 2024-04-10T22:45:10Z |
| format | Article |
| id | doaj.art-a5f7fd4d1ec14f8a9408162e7c0a4594 |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-04-10T22:45:10Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-a5f7fd4d1ec14f8a9408162e7c0a45942023-01-15T12:21:34ZengBMCBMC Biology1741-70072023-01-0121111610.1186/s12915-022-01502-0CD4+ and CD8+ regulatory T cell characterization in the rat using a unique transgenic Foxp3-EGFP modelSéverine Ménoret0Laurent Tesson1Séverine Remy2Victor Gourain3Céline Sérazin4Claire Usal5Aude Guiffes6Vanessa Chenouard7Laure-Hélène Ouisse8Malika Gantier9Jean-Marie Heslan10Cynthia Fourgeux11Jeremie Poschmann12Carole Guillonneau13Ignacio Anegon14Nantes Université, CHU Nantes, Inserm, CNRS, SFR Santé, Inserm UMS 016 CNRS UMS 3556INSERM, Centre de Recherche en Transplantation et Immunologie UMR1064, Nantes UniversitéINSERM, Centre de Recherche en Transplantation et Immunologie UMR1064, Nantes UniversitéNantes Université, CHU Nantes, Inserm, CNRS, SFR Santé, Inserm UMS 016 CNRS UMS 3556INSERM, Centre de Recherche en Transplantation et Immunologie UMR1064, Nantes UniversitéINSERM, Centre de Recherche en Transplantation et Immunologie UMR1064, Nantes UniversitéINSERM, Centre de Recherche en Transplantation et Immunologie UMR1064, Nantes UniversitéINSERM, Centre de Recherche en Transplantation et Immunologie UMR1064, Nantes UniversitéINSERM, Centre de Recherche en Transplantation et Immunologie UMR1064, Nantes UniversitéINSERM, Centre de Recherche en Transplantation et Immunologie UMR1064, Nantes UniversitéINSERM, Centre de Recherche en Transplantation et Immunologie UMR1064, Nantes UniversitéINSERM, Centre de Recherche en Transplantation et Immunologie UMR1064, Nantes UniversitéINSERM, Centre de Recherche en Transplantation et Immunologie UMR1064, Nantes UniversitéINSERM, Centre de Recherche en Transplantation et Immunologie UMR1064, Nantes UniversitéINSERM, Centre de Recherche en Transplantation et Immunologie UMR1064, Nantes UniversitéAbstract Background Regulatory T cells (Treg) in diverse species include CD4+ and CD8+ T cells. In all species, CD8+ Treg have been only partially characterized and there is no rat model in which CD4+ and CD8+ FOXP3+ Treg are genetically tagged. Results We generated a Foxp3-EGFP rat transgenic line in which FOXP3 gene was expressed and controlled EGFP. CD4+ and CD8+ T cells were the only cells that expressed EGFP, in similar proportion as observed with anti-FOXP3 antibodies and co-labeled in the same cells. CD4+EGFP+ Treg were 5–10 times more frequent than CD8+EGFP+ Treg. The suppressive activity of CD4+ and CD8+ Treg was largely confined to EGFP+ cells. RNAseq analyses showed similarities but also differences among CD4+ and CD8+ EGFP+ cells and provided the first description of the natural FOXP3+CD8+ Treg transcriptome. In vitro culture of CD4+ and CD8+ EGFP− cells with TGFbeta and IL-2 generated induced EGFP+ Treg. CD4+ and CD8+ EGFP+ Treg were expanded upon in vivo administration of a low dose of IL-2. Conclusions This new and unique rat line constitutes a useful model to identify and isolate viable CD4+ and CD8+ FOXP3+ Treg. Additionally, it allows to identify molecules expressed in CD8+ Treg that may allow to better define their phenotype and function not only in rats but also in other species.https://doi.org/10.1186/s12915-022-01502-0Immune toleranceGenome editingGene knockinFoxp3CD4+ TregCD8+ Treg |
| spellingShingle | Séverine Ménoret Laurent Tesson Séverine Remy Victor Gourain Céline Sérazin Claire Usal Aude Guiffes Vanessa Chenouard Laure-Hélène Ouisse Malika Gantier Jean-Marie Heslan Cynthia Fourgeux Jeremie Poschmann Carole Guillonneau Ignacio Anegon CD4+ and CD8+ regulatory T cell characterization in the rat using a unique transgenic Foxp3-EGFP model BMC Biology Immune tolerance Genome editing Gene knockin Foxp3 CD4+ Treg CD8+ Treg |
| title | CD4+ and CD8+ regulatory T cell characterization in the rat using a unique transgenic Foxp3-EGFP model |
| title_full | CD4+ and CD8+ regulatory T cell characterization in the rat using a unique transgenic Foxp3-EGFP model |
| title_fullStr | CD4+ and CD8+ regulatory T cell characterization in the rat using a unique transgenic Foxp3-EGFP model |
| title_full_unstemmed | CD4+ and CD8+ regulatory T cell characterization in the rat using a unique transgenic Foxp3-EGFP model |
| title_short | CD4+ and CD8+ regulatory T cell characterization in the rat using a unique transgenic Foxp3-EGFP model |
| title_sort | cd4 and cd8 regulatory t cell characterization in the rat using a unique transgenic foxp3 egfp model |
| topic | Immune tolerance Genome editing Gene knockin Foxp3 CD4+ Treg CD8+ Treg |
| url | https://doi.org/10.1186/s12915-022-01502-0 |
| work_keys_str_mv | AT severinemenoret cd4andcd8regulatorytcellcharacterizationintheratusingauniquetransgenicfoxp3egfpmodel AT laurenttesson cd4andcd8regulatorytcellcharacterizationintheratusingauniquetransgenicfoxp3egfpmodel AT severineremy cd4andcd8regulatorytcellcharacterizationintheratusingauniquetransgenicfoxp3egfpmodel AT victorgourain cd4andcd8regulatorytcellcharacterizationintheratusingauniquetransgenicfoxp3egfpmodel AT celineserazin cd4andcd8regulatorytcellcharacterizationintheratusingauniquetransgenicfoxp3egfpmodel AT claireusal cd4andcd8regulatorytcellcharacterizationintheratusingauniquetransgenicfoxp3egfpmodel AT audeguiffes cd4andcd8regulatorytcellcharacterizationintheratusingauniquetransgenicfoxp3egfpmodel AT vanessachenouard cd4andcd8regulatorytcellcharacterizationintheratusingauniquetransgenicfoxp3egfpmodel AT laureheleneouisse cd4andcd8regulatorytcellcharacterizationintheratusingauniquetransgenicfoxp3egfpmodel AT malikagantier cd4andcd8regulatorytcellcharacterizationintheratusingauniquetransgenicfoxp3egfpmodel AT jeanmarieheslan cd4andcd8regulatorytcellcharacterizationintheratusingauniquetransgenicfoxp3egfpmodel AT cynthiafourgeux cd4andcd8regulatorytcellcharacterizationintheratusingauniquetransgenicfoxp3egfpmodel AT jeremieposchmann cd4andcd8regulatorytcellcharacterizationintheratusingauniquetransgenicfoxp3egfpmodel AT caroleguillonneau cd4andcd8regulatorytcellcharacterizationintheratusingauniquetransgenicfoxp3egfpmodel AT ignacioanegon cd4andcd8regulatorytcellcharacterizationintheratusingauniquetransgenicfoxp3egfpmodel |