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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...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
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
Descripción
Sumario: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.