IL-7 producing immunotherapy improves ex vivo T cell functions of immunosenescent patients, especially post hip fracture
Following acute stress such as trauma or sepsis, most of critically ill elderly patients become immunosuppressed and susceptible to secondary infections and enhanced mortality. We have developed a virus-based immunotherapy encoding human interleukin-7 (hIL-7) aiming at restoring both innate an adapt...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-08-01
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| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21645515.2023.2232247 |
| _version_ | 1827806291379093504 |
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| author | Chrystel Marton Alix Minaud Charles-Antoine Coupet Manon Chauvin Jamila Dhiab Hélène Vallet Jacques Boddaert Nadine Kehrer Bérangère Bastien Geneviève Inchauspe Luc Barraud Delphine Sauce |
| author_facet | Chrystel Marton Alix Minaud Charles-Antoine Coupet Manon Chauvin Jamila Dhiab Hélène Vallet Jacques Boddaert Nadine Kehrer Bérangère Bastien Geneviève Inchauspe Luc Barraud Delphine Sauce |
| author_sort | Chrystel Marton |
| collection | DOAJ |
| description | Following acute stress such as trauma or sepsis, most of critically ill elderly patients become immunosuppressed and susceptible to secondary infections and enhanced mortality. We have developed a virus-based immunotherapy encoding human interleukin-7 (hIL-7) aiming at restoring both innate an adaptative immune homeostasis in these patients. We assessed the impact of this encoded hIL-7 on the ex vivo immune functions of T cells from PBMC of immunosenescent patients with or without hip fracture. T-cell ex vivo phenotyping was characterized in terms of senescence (CD57), IL-7 receptor (CD127) expression, and T cell differentiation profile. Then, post stimulation, activation status, and functionality (STAT5/STAT1 phosphorylation and T cell proliferation assays) were evaluated by flow cytometry. Our data show that T cells from both groups display immunosenescence features, express CD127 and are activated after stimulation by virotherapy-produced hIL-7-Fc. Interestingly, hip fracture patients exhibit a unique functional ability: An important T cell proliferation occurred compared to controls following stimulation with hIL-7-Fc. In addition, stimulation led to an increased naïve T cell as well as a decreased effector memory T cell proportions compared to controls. This preliminary study indicates that the produced hIL-7-Fc is well recognized by T cells and initiates IL-7 signaling through STAT5 and STAT1 phosphorylation. This signaling efficiently leads to T cell proliferation and activation and enables a T cell “rejuvenation.” These results are in favor of the clinical development of the hIL-7-Fc expressing virotherapy to restore or induce immune T cell responses in immunosenescent hip fracture patients. |
| first_indexed | 2024-03-11T21:39:06Z |
| format | Article |
| id | doaj.art-ccda096e0721408d960d302a97a3c0b1 |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T21:39:06Z |
| publishDate | 2023-08-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-ccda096e0721408d960d302a97a3c0b12023-09-26T13:25:51ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2023-08-0119210.1080/21645515.2023.22322472232247IL-7 producing immunotherapy improves ex vivo T cell functions of immunosenescent patients, especially post hip fractureChrystel Marton0Alix Minaud1Charles-Antoine Coupet2Manon Chauvin3Jamila Dhiab4Hélène Vallet5Jacques Boddaert6Nadine Kehrer7Bérangère Bastien8Geneviève Inchauspe9Luc Barraud10Delphine Sauce11Sorbonne Université, InsermSorbonne Université, InsermTransgeneSorbonne Université, InsermSorbonne Université, InsermSorbonne Université, InsermSorbonne Université, InsermTransgeneTransgeneTransgeneTransgeneSorbonne Université, InsermFollowing acute stress such as trauma or sepsis, most of critically ill elderly patients become immunosuppressed and susceptible to secondary infections and enhanced mortality. We have developed a virus-based immunotherapy encoding human interleukin-7 (hIL-7) aiming at restoring both innate an adaptative immune homeostasis in these patients. We assessed the impact of this encoded hIL-7 on the ex vivo immune functions of T cells from PBMC of immunosenescent patients with or without hip fracture. T-cell ex vivo phenotyping was characterized in terms of senescence (CD57), IL-7 receptor (CD127) expression, and T cell differentiation profile. Then, post stimulation, activation status, and functionality (STAT5/STAT1 phosphorylation and T cell proliferation assays) were evaluated by flow cytometry. Our data show that T cells from both groups display immunosenescence features, express CD127 and are activated after stimulation by virotherapy-produced hIL-7-Fc. Interestingly, hip fracture patients exhibit a unique functional ability: An important T cell proliferation occurred compared to controls following stimulation with hIL-7-Fc. In addition, stimulation led to an increased naïve T cell as well as a decreased effector memory T cell proportions compared to controls. This preliminary study indicates that the produced hIL-7-Fc is well recognized by T cells and initiates IL-7 signaling through STAT5 and STAT1 phosphorylation. This signaling efficiently leads to T cell proliferation and activation and enables a T cell “rejuvenation.” These results are in favor of the clinical development of the hIL-7-Fc expressing virotherapy to restore or induce immune T cell responses in immunosenescent hip fracture patients.http://dx.doi.org/10.1080/21645515.2023.2232247immunosenescencehip fractureimmunotherapyvirotherapyinterleukin-7t-cell functionstraumaimmunosuppressioncytokine |
| spellingShingle | Chrystel Marton Alix Minaud Charles-Antoine Coupet Manon Chauvin Jamila Dhiab Hélène Vallet Jacques Boddaert Nadine Kehrer Bérangère Bastien Geneviève Inchauspe Luc Barraud Delphine Sauce IL-7 producing immunotherapy improves ex vivo T cell functions of immunosenescent patients, especially post hip fracture Human Vaccines & Immunotherapeutics immunosenescence hip fracture immunotherapy virotherapy interleukin-7 t-cell functions trauma immunosuppression cytokine |
| title | IL-7 producing immunotherapy improves ex vivo T cell functions of immunosenescent patients, especially post hip fracture |
| title_full | IL-7 producing immunotherapy improves ex vivo T cell functions of immunosenescent patients, especially post hip fracture |
| title_fullStr | IL-7 producing immunotherapy improves ex vivo T cell functions of immunosenescent patients, especially post hip fracture |
| title_full_unstemmed | IL-7 producing immunotherapy improves ex vivo T cell functions of immunosenescent patients, especially post hip fracture |
| title_short | IL-7 producing immunotherapy improves ex vivo T cell functions of immunosenescent patients, especially post hip fracture |
| title_sort | il 7 producing immunotherapy improves ex vivo t cell functions of immunosenescent patients especially post hip fracture |
| topic | immunosenescence hip fracture immunotherapy virotherapy interleukin-7 t-cell functions trauma immunosuppression cytokine |
| url | http://dx.doi.org/10.1080/21645515.2023.2232247 |
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