Altered Innate-like T Cell Development in Vα14-Jα18 TCRα Transgenic Mice
Autor: | Qiaochu Lin, Carolina de Amat Herbozo, Meggie Kuypers, Thierry Mallevaey, Christophe Paget, Irene Lau |
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Přispěvatelé: | University of Toronto, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), PAGET, Christophe, Gonzalez, Loïc, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM) |
Rok vydání: | 2020 |
Předmět: |
Genetically modified mouse
Transgene T cell [SDV]Life Sciences [q-bio] Immunology Receptors Antigen T-Cell Stimulation Galactosylceramides Mice Transgenic Thymus Gland Biology CD8-Positive T-Lymphocytes 03 medical and health sciences Mice 0302 clinical medicine medicine Immunology and Allergy Animals 030304 developmental biology 0303 health sciences Cell growth T-cell receptor Cell Differentiation General Medicine T-Lymphocytes Helper-Inducer Cell biology [SDV] Life Sciences [q-bio] Mice Inbred C57BL Thymocyte medicine.anatomical_structure Models Animal Natural Killer T-Cells Antigens CD1d CD8 030215 immunology |
Zdroj: | ImmunoHorizons ImmunoHorizons, The American Association of Immunologists, Inc, 2020, 4 (12), pp.797-808. ⟨10.4049/immunohorizons.2000100⟩ |
ISSN: | 2573-7732 |
Popis: | CD1d-restricted invariant NKT (iNKT) cells are innate-like T cells that respond to glycolipids, a class of Ags that are invisible to conventional T cells. iNKT cells develop in the thymus where they receive strong “agonist” TCR signals. During their ontogeny, iNKT cells differentiate into discrete iNKT1, iNKT2, and iNKT17 effector subsets akin to helper CD4 T cells. In this study, we found that transgenic (Tg) expression of the canonical Vα14-Jα18 TCRα-chain at the double-positive thymocyte stage led to premature iNKT cell development and a cell-intrinsic bias toward iNKT2 cells, due to increased TCR signaling upon selection. Consistent with the strong iNKT2 bias, innate memory CD8+ T cells were found in greater numbers in Vα14 Tg mice, whereas the prevalence of mucosa-associated invariant T cells was reduced. iNKT cells from Vα14 Tg mice were hyporesponsive to stimulation by their cognate Ag α-galactosylceramide. Finally, Vα14 Tg mice displayed increased B16F10 melanoma tumor growth compared with wild-type mice. This study reveals some of the limitations of Vα14 Tg mice and warrants the cautious interpretation of past and future findings using this mouse model. |
Databáze: | OpenAIRE |
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