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Generation of functional human T cell development in NOD/SCID/IL2rγ(null) humanized mice without using fetal tissue: Application as a model of HIV infection and persistence
Humanization of mice with functional T cells currently relies on co-implantation of hematopoietic stem cells from fetal liver and autologous fetal thymic tissue (so-called BLT mouse model). Here, we show that NOD/SCID/IL2rγ(null) mice humanized with cord blood- derived CD34(+) cells and implanted wi...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9969074/ https://www.ncbi.nlm.nih.gov/pubmed/36736326 http://dx.doi.org/10.1016/j.stemcr.2023.01.003 |
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author | Colas, Chloé Volodina, Olga Béland, Kathie Pham, Tram N.Q. Li, Yuanyi Dallaire, Frédéric Soulard, Clara Lemieux, William Colamartino, Aurélien B.L. Tremblay-Laganière, Camille Dicaire, Renée Guimond, Jean Vobecky, Suzanne Poirier, Nancy Patey, Natasha Cohen, Éric A. Haddad, Elie |
author_facet | Colas, Chloé Volodina, Olga Béland, Kathie Pham, Tram N.Q. Li, Yuanyi Dallaire, Frédéric Soulard, Clara Lemieux, William Colamartino, Aurélien B.L. Tremblay-Laganière, Camille Dicaire, Renée Guimond, Jean Vobecky, Suzanne Poirier, Nancy Patey, Natasha Cohen, Éric A. Haddad, Elie |
author_sort | Colas, Chloé |
collection | PubMed |
description | Humanization of mice with functional T cells currently relies on co-implantation of hematopoietic stem cells from fetal liver and autologous fetal thymic tissue (so-called BLT mouse model). Here, we show that NOD/SCID/IL2rγ(null) mice humanized with cord blood- derived CD34(+) cells and implanted with allogeneic pediatric thymic tissues excised during cardiac surgeries (CCST) represent an alternative to BLT mice. CCST mice displayed a strong immune reconstitution, with functional T cells originating from CD34(+) progenitor cells. They were equally susceptible to mucosal or intraperitoneal HIV infection and had significantly higher HIV-specific T cell responses. Antiretroviral therapy (ART) robustly suppressed viremia and reduced the frequencies of cells carrying integrated HIV DNA. As in BLT mice, we observed a complete viral rebound following ART interruption, suggesting the presence of HIV reservoirs. In conclusion, CCST mice represent a practical alternative to BLT mice, broadening the use of humanized mice for research. |
format | Online Article Text |
id | pubmed-9969074 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-99690742023-02-28 Generation of functional human T cell development in NOD/SCID/IL2rγ(null) humanized mice without using fetal tissue: Application as a model of HIV infection and persistence Colas, Chloé Volodina, Olga Béland, Kathie Pham, Tram N.Q. Li, Yuanyi Dallaire, Frédéric Soulard, Clara Lemieux, William Colamartino, Aurélien B.L. Tremblay-Laganière, Camille Dicaire, Renée Guimond, Jean Vobecky, Suzanne Poirier, Nancy Patey, Natasha Cohen, Éric A. Haddad, Elie Stem Cell Reports Resource Humanization of mice with functional T cells currently relies on co-implantation of hematopoietic stem cells from fetal liver and autologous fetal thymic tissue (so-called BLT mouse model). Here, we show that NOD/SCID/IL2rγ(null) mice humanized with cord blood- derived CD34(+) cells and implanted with allogeneic pediatric thymic tissues excised during cardiac surgeries (CCST) represent an alternative to BLT mice. CCST mice displayed a strong immune reconstitution, with functional T cells originating from CD34(+) progenitor cells. They were equally susceptible to mucosal or intraperitoneal HIV infection and had significantly higher HIV-specific T cell responses. Antiretroviral therapy (ART) robustly suppressed viremia and reduced the frequencies of cells carrying integrated HIV DNA. As in BLT mice, we observed a complete viral rebound following ART interruption, suggesting the presence of HIV reservoirs. In conclusion, CCST mice represent a practical alternative to BLT mice, broadening the use of humanized mice for research. Elsevier 2023-02-02 /pmc/articles/PMC9969074/ /pubmed/36736326 http://dx.doi.org/10.1016/j.stemcr.2023.01.003 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Resource Colas, Chloé Volodina, Olga Béland, Kathie Pham, Tram N.Q. Li, Yuanyi Dallaire, Frédéric Soulard, Clara Lemieux, William Colamartino, Aurélien B.L. Tremblay-Laganière, Camille Dicaire, Renée Guimond, Jean Vobecky, Suzanne Poirier, Nancy Patey, Natasha Cohen, Éric A. Haddad, Elie Generation of functional human T cell development in NOD/SCID/IL2rγ(null) humanized mice without using fetal tissue: Application as a model of HIV infection and persistence |
title | Generation of functional human T cell development in NOD/SCID/IL2rγ(null) humanized mice without using fetal tissue: Application as a model of HIV infection and persistence |
title_full | Generation of functional human T cell development in NOD/SCID/IL2rγ(null) humanized mice without using fetal tissue: Application as a model of HIV infection and persistence |
title_fullStr | Generation of functional human T cell development in NOD/SCID/IL2rγ(null) humanized mice without using fetal tissue: Application as a model of HIV infection and persistence |
title_full_unstemmed | Generation of functional human T cell development in NOD/SCID/IL2rγ(null) humanized mice without using fetal tissue: Application as a model of HIV infection and persistence |
title_short | Generation of functional human T cell development in NOD/SCID/IL2rγ(null) humanized mice without using fetal tissue: Application as a model of HIV infection and persistence |
title_sort | generation of functional human t cell development in nod/scid/il2rγ(null) humanized mice without using fetal tissue: application as a model of hiv infection and persistence |
topic | Resource |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9969074/ https://www.ncbi.nlm.nih.gov/pubmed/36736326 http://dx.doi.org/10.1016/j.stemcr.2023.01.003 |
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